The formation of stones made of uric acid (or urates) results from metabolic issues which we will review below. The Dalmatian is uniquely predisposed to stone formation because of an equally unique liver and kidney biochemistry. The gene that causes some Dalmatians to form stones seems to also be in the English Bulldog, though not nearly to the same extent. Because uric acid stones are formed in patients with congenital liver shunts, when they are found in breeds other than Dalmatians or English Bulldogs they warrant a liver workup.
The Biochemistry of the Uric Acid Stone
Uric acid stones. Photo by MarVistaVet
It all starts with biochemicals called purines. There are three types of purines:
- Oxypurines - like xanthine, hypoxanthine, uric acid, and allantoin - words with which the Dalmatian owner should become familiar
- Aminopurines - like adenine and guanine that make up DNA
- Methylpurines - like caffeine and theophylline, which are drugs
We eat purines when we eat meat and drink them with coffee. Our livers convert them ultimately into something called “allantoin,” one of the oxypurines mentioned above, which readily dissolves in the body's fluids and is easy for us to unload in that waste/water mixture known as urine.
Purine to Allantoin Pathway
Purine to Allantoin Pathway Diagram by MarVista Vet
This system works for all just about all mammals except for Dalmatians. Dalmatians are different.
How Dalmatians Get Rid of Purines
Dalmatians just cannot seem to convert uric acid to allantoin; the process described above never gets past the uric acid stage. Dalmatian liver cells simply cannot absorb uric acid, which is where the conversion to allantoin ought to take place. Dalmatians must excrete uric acid in their urine without this last conversion, and the problem is that the stuff just is not very water-soluble. Being unable to convert uric acid to allantoin is the main predisposing factor for uric acid stone formation and accounts for why 80% of uric acid bladder stones come from Dalmatians. The other 20% are from other breeds with the same genetic mutation as stone-forming Dalmatians or patients with impaired liver function.
Purines to Uric Acid Pathway
Purines to Uric Acid Pathway by MarVista Vet
Is this the same as Gout in Humans?
Not really, but it is similar. Humans with gout have an excess of uric acid in their bodies for a number of reasons:
- Excessive consumption of high-purine foods (alcohol, shellfish, mushrooms, spinach, etc.)
- Certain medications may increase uric acid levels in the bloodstream.
- Hereditary factors also exist.
Uric acid crystals form and congeal into kidney stones but classically gout involves the precipitation of uric acid crystals in the delicate membranes of joints, causing arthritis pain. Dogs do not get joint uric acid deposits in the same way humans do; for dogs, the urinary tract is where the action is. As an aside, birds are not able to convert uric acid to allantoin (the crystalline white material that is eliminated by birds is actually their urine; the greyish material eliminated with the white is stool). Birds that make excess uric acid will develop uric acid joint deposits, essentially gout.
Do all Dalmatians form Uric Acid Stones?
No, only some Dalmatians form stones and we do not know what makes one Dalmatian a stone former and another one clinically normal, except that those that form stones circulate extra high levels of uric acid compared to other Dalmatians. There are genetic factors, dietary factors, and unknown factors. We know that male Dalmatians are reported as stone formers more often than female Dalmatians but this may be a reflection of the fact that only male dogs have the added stone complication of urethral obstruction, a problem female dogs rarely have to worry about (thus male dogs may be seeing the vet for their stones more than female dogs do). Stone-forming Dalmatians seem to be excreting more uric acid than their non-stone-forming counterparts. The average age at which a Dalmatian first is found to have stones is 4.5 years. The risk of stone formation declines as the dog ages. Overall it appears that even though all Dalmatians excrete high amounts of uric acid, less than 10% of Dalmatians actually form stones.
As for non-Dalmatians, in the absence of liver disease a genetic mutation is necessary to form uric acid stones. We can now genetically test for this mutation though this is not helpful for the Dalmatian since we already know they have the mutation. Learn more information about this genetic test.
There has been a movement to breed Dalmatians that do not have the problematic mutation. This project originally involved crossing a Dalmatian with a pointer and then breeding the progeny with purebred Dalmatians for numerous generations following. The result is a dog that is over 99% genetically the same as a purebred Dalmatian but without the uric acid mutation. Until 2011, these dogs were not recognized as Dalmatians by the American Kennel Club but, happily, now they are.
How Do You Know if Your Dalmatian Has Stones?
Hopefully, this is an issue that will never come up but the following are signs of irritation in the lower urinary tract, which would indicate a need to search for stones:
- Bloody urine
- Straining to urinate
- Urinating small amounts frequently
- Seeing gritty material in the dog's urine
Uric acid stones may or may not be visible on plain radiographs. Often ultrasound or contrast radiography (use of urinary dyes to create a double contrast cystogram) is needed to see the stones.
Uric acid crystals are abnormal findings in the urine of dogs other than Dalmatians. In the Dalmatian, because of their unique metabolism, uric acid crystals are normal in any urine sample and do not indicate whether stones are present or not.
Getting Rid of the Stones
Urinary obstruction is an emergency!
Radiograph of an os penis.
Small black dots are tiny uric acid stones surrounded by
urinary dye. These stones are obstructing urine flow.
Photo courtesy of Dr. William Blevins
If you have a male dog straining to urinate, bring him to the vet right away. He may have stones obstructing his urethra (the passageway for urine in the male dog goes through a bone called the os penis and stones often catch at this location). If this has occurred, a urinary catheter must be used to push the stone back into the urinary bladder where it can either be removed or dissolved.
Stone Removal via Surgery
Surgery is the fastest way to remove bladder stones but also the most invasive way and probably most expensive way. The bladder is surgically opened and the stones are removed and sent to the lab for analysis (Dalmatians are perfectly capable of forming struvite and oxalate stones as well so analysis must be done to determine the type of stones that have formed.) The urinary tract is flushed to get all stones out including those hiding in the urethra. The bladder is closed and tested for leaks. The belly is closed and the patient generally goes home in a day or two depending on their ability to urinate and their appetite. This all sounds simple but there are disadvantages.
- Surgery is relatively expensive.
- Anesthesia is not without risk, though with modern monitoring equipment risks have been minimized.
- Dalmatians with uric acid stones may have hundreds of small stones and may also have stones actually embedded in the bladder wall. It may not be possible to get them all out. (If this happens, the remaining stones may be handled by dissolution - in other words, we have to make the remaining stones dissolve).
- The bladder may not heal normally (a rare complication but a possible one), and leaks in the urinary tract can be life-threatening.
In general, surgery is a low-risk procedure and but it is not unusual for a Dalmatian to require several stone-removing surgeries during his or her lifetime.
Stone Removal via Dissolution
The idea here is to create urine that brings the uric acid of the existing stone back into solution (essentially dissolving the stones). There are several steps here:
- First, any bladder infection must be controlled. An infection will interfere with creating the desired urine pH and may even create struvite bladder stones. The urine should be cultured and if an organism grows, the patient should be on antibiotics until the urine cultures negative and possibly throughout the entire duration of the stone dissolution process.
- For years there was one therapeutic diet restrictive enough in purines to be appropriate for stone dissolution; it should be noted that this diet is not appropriate for puppies and if a growing dog has uric acid stones, surgery removal is probably a better choice). The canned version is felt to be superior to the kibble as feeding canned food adds water to the diet - and ultimately to the urine - which helps dilute the uric acid. Another manufacturer now offers a low-purine diet for uric acid-forming breeds, and it is available as a dry food.
- A medication called allopurinol must be given twice a day at a dose appropriate for dissolving uric acid stones. After the stones have been dissolved, a lower dose of allopurinol is used for prevention and maintenance. This medication is important in uric acid stone management. Read more information about allopurinol on side effects, drug interactions, and general information.
- Further alkalinization of urine beyond what occurs with a therapeutic low-purine diet may or may not be necessary. The goal urine pH is neutral (7.0), and some owners may wish to obtain urine dipsticks to monitor this at home. Excess alkalinization may promote the development of oxalate stones, which we certainly do not want, and inadequate alkalinization will prevent dissolution. A periodical urinalysis can check to see if any further steps in regard to urine pH control are needed.
After a month of this protocol, the stones are re-radiographed to compare their size and number to those on the original radiograph, and urinalysis is performed to assess pH and look for crystals. (Stones not visible on radiographs must be assessed by ultrasound, which is generally more costly.) If the stones are getting smaller, the protocol is continued. If they are gone, the patient switches to prevention. If there are more stones or they are bigger, it is possible that xanthine stones are being formed (see below) and some small stones or urine sediment samples should be retrieved by catheter for analysis. It may simply be that there was cheating on the diet or that the allopurinol dose must be increased.
The disadvantages of stone removal by dissolution are:
- It can take months to dissolve uric acid bladder stones.
- The protocol may not work.
- The expense of radiographs (or ultrasound) and urinalysis every month eventually will be more than the surgery would have been if the stones do not quickly dissolve.
- If the dog is male, the stones may become small enough to obstruct the urethra (an emergency), which requires the use of a urinary catheter to push the stone back into the bladder.
The average dog dissolves stones in three to four months.
Allopurinol: The Short Version
Recall the original purine metabolism pathway:
Purine to Allantoin Pathway
Purine to Allantoin Pathway Diagram by MarVista Vet
We already know that Dalmatians stop at uric acid. Allopurinol is a medication that binds and shuts down an enzyme called xanthine oxidase; this is the enzyme that takes hypoxanthine to xanthine and ultimately to uric Acid. Without xanthine oxidase, purines are stuck in the Hypoxanthine stage and do not make it to Uric Acid. This sounds like exactly what we want to do but it is important to keep in mind that the inhibition of xanthine oxidase means an increase in xanthine and hypoxanthine. It can actually mean the formation of xanthine stones especially if there is cheating on the diet. In fact, let us emphasize:
The combination of cheating on the diet and using allopurinol is likely to lead to xanthine bladder stones!
If you know there will be cheating on the diet, it is probably best not to use allopurinol.
Allopurinol is dangerous in animals with poor kidney function.
Now that the Stones are Gone: Prevention and Monitoring
Uric Acid Stones
The diet of the stone-forming dog is the most important factor in preventing future episodes of stones. Our goal is to feed a diet low in purines and create alkaline urine (which is best to keep uric acid in solution). This is done by feeding a low salt, low purine diet; again, discuss with your veterinarian which is best for your pet.
The following foods are considered virtually purine-free and can be used as treats for stone-forming dogs:
- Whole-grain cereals (as long as they do not contain yeast)
Allopurinol is generally required for prevention but at a lower dose than required to dissolve existing stones. Be sure to familiarize yourself with this medication as dietary cheating commonly leads to the formation of xanthine stones.
As for periodic monitoring to be sure no new stones are likely to form, several protocols have been advocated.
- A urinalysis should be done one month after instituting prevention and every three to six months thereafter. Imaging with ultrasound or with radiographs with contrast dye should be considered every six months or more often if there are recurring urinary symptoms. It is important to detect new stones while they are still small enough to pass. If stones are small, they can be flushed from the bladder without surgery. This is a very complete method but all that ultrasound/contrast radiography may be expensive.
- The 24-hour uric acid production test involves collecting all the urine a dog produces over either a 12-hour period and multiplying the value by two, or collecting 24 hours of urine. This typically involves some kind of urine collection bag and a urinary catheter sewn in place (or a very cooperative dog). It is difficult to keep a urinary collection system in place in a normal dog and thus this test is problematic to run. The urine is collected and sent to the lab, and the total production of uric acid is determined. This will tell if the dog is on track to avoid future stones or not. Because the collection is so difficult, many skip it and simply do the above monitoring. The goal value is less than 300 mg/kg of body weight daily.
- The uric acid (or urate) to creatinine ratio test. The idea here was to use a single urine sample to get an idea of how much uric acid the dog was producing. This ratio seemed like a good idea at the time and was certainly easier than the 24-hour urine collection but it has not panned out as a valid test to predict stone re-formation but will tell the veterinarian if the pet owner is cheating on the diet.
- The blood urea nitrogen level (BUN) is a common parameter assessing kidney function. In most cases, we are concerned about its being elevated but in monitoring stone-forming Dalmatians, a lower than normal BUN (ideally, less than 10mg/dl) indicates that no dietary cheating is going on.
Your veterinarian is likely to pick and choose from these tests to put together a protocol they are comfortable with that fits your budget.
Off Limits for Stone-Forming Dalmatians
- Brewer's yeast supplements have been popular (though ineffective) for flea control and generally represent a tasty B vitamin supplement for dogs. This supplement is high in purines and not appropriate for stone-forming Dalmatians.
- Vitamin C is a common supplement for dogs, especially in joint health nutritional products. Vitamin C is likely to overly acidify the urine of a stone-forming Dalmatian and should not be used.
- Certain cancer chemotherapy protocols involve interactions with allopurinol and must be modified.
No one has formally studied the effect of joint nutriceuticals on urine pH. If you want to use glucosamine or other products on an arthritic stone-forming Dalmatian, the urine pH will require monitoring to be sure excess urine acidification has not occurred.