Canine Cystinuria

This month’s B-Naturals Newsletter is written by a wonderful guest author, Christie Keith, who is well known for being a contributing editor at Pet Connection, a pet columnist for the San Francisco Chronicle and her work with PetHobbiest.com. She has her own personal website, www.caberfeidh.com, with information on her Scottish Deerhounds and a wealth of excellent health articles. I am delighted she has agreed to write on Canine Cystinuria this month and I hope you all find this information informative and interesting. While Canine Cystinuria is not a common disorder in dogs, it is genetic and can cause serious health problems.

By Christie Keith

Cystinuria is a genetic defect in the kidney tubules; it can affect dogs, humans, and a few other species.

Normal kidneys filter the amino acid cystine and do not allow it to go into the urine. In individuals with cystinuria, this filtering action fails, and cystine passes into the urine, where it can form crystals and/or stones (uroliths). If stones form, they can block the urethra and obstruct urinary flow, especially in males.

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There are at least two types of cystinuria that affect dogs, and one of them does not seem to occur in females at all. The other, which affects the Newfoundland and Labrador Retriever and perhaps some other breeds and mixes, is common in both males and females, however, females are less likely to obstruct due to their wider urinary passage.

Dogs who have this defect are born with it, although it can take years to cause symptoms – or never cause any. The Textbook of Internal Veterinary Medicine says, "Not all cystinuric dogs form uroliths; therefore, cystinuria is a predisposing rather than a primary cause of cystine urolith formation. In a study of five generations of offspring from one Scottish terrier, only one of six cystinuric males formed uroliths."

This can make cystinuria a particularly frustrating condition to manage, as even a dog known to have cystinuria may go his whole life without obstructing, while another dog, never diagnosed, can have a life-threatening obstruction as his first symptom. It's not known at this time why some dogs with cystinuria form stones and others do not. Genetic factors probably have the greatest influence on whether or not a dog with cystinuria is a stone former, but there are probably unknown environmental factors involved as well.

Obviously, knowing your dog has cystinuria can enable you to be particularly vigilant for symptoms of obstruction such as restricted urinary flow, reluctance to urinate, or bloody urine. And owners of Newfoundlands, Labradors, and possibly some mixed breeds, can find out if their dog is affected. In those breeds, cystinuria is an autosomal recessive trait, and there is a simple (http://w3.vet.upenn.edu/research/centers/penngen/services/deublerlab/cystinuria.html) genetic test that reliably determines if a dog is affected by, or carries, cystinuria.

Unfortunately, the mode of inheritance is unknown in other breeds, does not appear to be autosomal recessive, and there is no genetic test for the condition.

Diagnosis

It is currently possible to screen the urine of dogs for the presence of cystine, which is considered reliably diagnostic for cystinuria, as normal urine has no, or virtually no, cystine present.

There are three urine tests that can detect cystine. The first is a basic urinalysis. This is only reliable if cystine is present; a negative result doesn't mean your dog does not have cystinuria, but a positive result means he does. This is the least reliable test but the most readily available. Any vet's office can do a urinalysis.

The next-most-reliable test is the (http://research.vet.upenn.edu/SubmitaSample/tabid/554/Default.aspx) nitroprusside test being performed at the University of Pennsylvania. Owners can submit urine for testing without a vet and the cost is minimal, although overnight shipping and special packaging add substantially to the expense.

However, just as with a urinalysis, the nitroprusside test is only reliable if it's positive. A negative test does not mean your dog does not have cystinuria. There is no set number of tests that will "clear" your dog, and no age at which the test can be considered definitive if negative. Since the test is inexpensive and non-invasive, most breeders do at least three for each dog before considering them clear, while still realizing even these three tests might be unreliable.

There is a third test, the urine amino acid quantitation test, or quantitative amino acid analysis, which is performed only in a human medical laboratory. It is extremely expensive but is the most accurate. However, again, a negative test result is not absolutely definitive. Owners interested in this test should contact the University of Pennsylvania and try to arrange testing; a special rate may or may not be available if you go through them. Dr. Paula Henthorn is conducting research on canine cystinuria at the University of Pennsylvania and her address is:

Paula Henthorn Ph.D.

Associate Professor of Medical Genetics

3900 Delancey Street

School of Veterinary Medicine

University of Pennsylvania

Philadelphia, PA 19104-6010

Dr. Henthorn's office may be contacted by phone at 215-898-9601.

The current state of testing for this condition is best outlined by Dr. Henthorn in (http://web.archive.org/web/20070213000610/http://w3.vet.upenn.edu/research/centers/penngen/research/cystinuria_update.html) this article.

There is no question that the lack of a known mode of inheritance and a reliable screening test is a source of intense frustration for breeders.

Treatment and management

Even those dogs with a confirmed diagnosis are still difficult to manage. One reason for this is that the condition is extremely rare. Many veterinarians will go their entire careers without seeing a case, and will often rely on guidelines found in text books that are less than well-proven.

For example, because cystine is an amino acid, and amino acids are the building blocks of protein, a reduced-protein diet is usually prescribed for this condition. In fact, some 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, and will put intense pressure on their clients to put their dogs with cystinuria on such protocols.

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 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11467594&itool=iconabstr&query_hl=4) here.

On the (http://groups.yahoo.com/group/CanineCystinuria/) Canine Cystinuria email list, which I own, 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.

Furthermore, since cystine stones do not dissolve in alkaline urine, if the urine goes into acidity even briefly, stones can form and will not dissolve just because alkaline urine is achieved shortly thereafter.

The use of medications has been more successful. The drug Thiola is effective in preventing stone formation in many dogs, with few reported side effects. In fact, the single most frequently reported "side effect" is the depletion of the owner's bank account, especially for owners of large or giant breed dogs. Thiola is also an "orphan drug," and can be hard to obtain. Information on getting thiola is available from the FDA, (http://www.fda.gov/orphan/proceduresforthiola.pdf) here.

There is another drug that is easier to obtain and somewhat less expensive, cupramine (d-Penicillamine). This drug is associated with more side effects, but if your dog tolerates it, it might be a better choice.

Although it seems very extreme to some, many of us with stone-forming male dogs with cystinuria have had a procedure done on them called a "scrotal urethrostomy." In a nutshell, this is a surgery that redirects the dog's urethra away from the penis and out a new, surgically-created opening in front of the scrotum. This enables male dogs to more easily pass small stones, and can help prevent urinary blockage, the main risk from this condition. While it's not impossible they will still obstruct, it reduces the chances substantially. This surgery is not to be undertaken lightly, however.

The good news is that if your dog does not die of complications of his cystinuria, such as obstruction, recurrent infections, or surgical complications, there is no reason he won't live a normal lifespan. Many dogs, including stone formers and those who have had serious health problems when their condition was first diagnosed, have lived not just normal but longer-than-normal lives.

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.

If your dog has formed stones, the most important thing to understand is that this is a life-threatening emergency and requires immediate veterinary attention. You have to get those stones out of there and treat or prevent any urinary obstruction.

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 by the performance of a scrotal urethrostomy. 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 (http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00413.htm).

If the hydropulsion is successful and surgery is not an option or needs to be delayed, it is possible to dissolve the stones with Thiola. Existing cystine stones cannot be dissolved with diet or supplementation.

For more information on canine cystinuria, please visit http://www.caninecystinuria.com, or join the Canine Cystinuria email list at http://groups.yahoo.com/group/CanineCystinuria/.

Happy New Year to everyone and may 2010 bring much prosperity, good health and good fortune!