Uric Acid Stones/Urate Urolithiasis

Damation head medium mf

Uric Acid Stones

English Bulldog head 2

(photocredit: MorgueFile.com)

 

 

Formation of stones made of uric acid (or urates) result 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 present in the English Bulldog, though not nearly to the same extent. Uric acid stones also are formed in patients with congenital liver shunts and, in a breed other than the Dalmatian and English Bulldog, their presence warrants a liver work up.

THE BIOCHEMISTRY OF THE URIC ACID STONE:

It all starts with a biochemical called a “purine.” There are three types of purines:

  • Oxypurines (like xanthine, hypoxanthine, uric acid, and allantoin – words with which the Dalmatian owner should become very 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 when we drink coffee. Our livers convert them ultimately into something called “allantoin,” one of the oxypurines mentioned above, which is readily soluble in water and easy for us to unload in that waste/water mixture known as urine.

Purines convert to Hypoxanthine which converts to Xanthine
which converts to Uric Acid which converts to Allantoin.

This system works for just about all mammals except for Dalmatians. Dalmatians are different.

HOW DALMATIANS GET RID OF PURINES:

Dalmatians just cannot seem to convert uric acid all the way 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 to 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.

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.

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. For more information on this genetic test visit:

www.vgl.ucdavis.edu/services/Hyperuricosuria.php

There has been a movement to breed Dalmatians that do not have the problematic mutation. This 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 purebred Dalmatian but without the uric acid mutation. These dogs are not currently recognized as Dalmatians by the American Kennel Club but may fit the bill if showing and breeding is not the goal. For more information on "Low Uric Acid Dalmatians" visit:

www.luadalmatians.com

IS THIS THE SAME AS GOUT IN HUMANS?

Benjamin FranklinNot really, but it is similar. Humans with gout (such as Benjamin Franklin, a famous gout sufferer pictured on the left) 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 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.” 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.

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 search for stones should be made:

  • 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 special urinary dyes to create a “double contrast cystogram”) are needed to see the stones.

gall stones xray 1

Radiograph showing a urinary bladder full of stones (actually, these are oxalate stones, but it would
look the same if they were uric acid stones).

double contrast cystogram

Double contrast cystogram of Dalmatian
urinary bladder with uric acid stones. The black dots
show stones that are not visible on a normal radiograph.
This is a close up of a urinary bladder with contrast material inside. The contrast material (urinary dye) is white.
The surrounding air is black, and the black dots
inside the contrast material are the uric acid stones.
(Graphic by Dr. Bill Blevins. Used with permission)

Uric Acid crystals are an abnormal finding 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:

penis stones

Radiograph of an os penis
Small black dots are tiny uric acis stones surrounded by
urinary dye. These stones are obstructing urine flow.

Urinary obstruction is an emergency!

If you have a male dog straining to urinate, bring him to the vet right away. He may have stones obstructing his urethra (the passage way for urine in the male dog goes through an actual 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 an 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 his or her 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, remaining stones may be handled by dissolution).
     
  • 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 a urine which brings the uric acid of the existing stone back into solution. There are several steps here:

  • First, any bladder infection must be controlled. Infection will interfere with creating the desired urine pH and may even lead to the creation of 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 through out the entire duration of the stone dissolution process.
     
  • For years there was one diet restrictive enough in purines to be appropriate for stone dissolution: Hills U/d diet. (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). Canned U/d is felt to be superior to kibbled U/d as feeding canned food adds water to the diet (and ultimately to the urine) which helps dilute the uric acid. More recently Royal Canin has developed a diet specifically for uric acid forming breeds. It is called Urinary U/C low purine diet and is available as a dry food.

    Hills canine UD can

    Royal Canin canine Urinary UC bag


  • A medication called “Allopurinol” must be given twice a day at a special dose appropriate for dissolving uric acid stones. Allopurinol at lower doses is used in prevention of stone formation after the stones have been removed. Because of the importance of this medication in uric acid stone management we have included a special section on Allopurinol in our pharmacy library. Please click here to read this section which includes information on side effects, drug interactions, and general information.
     
  • Further alkalinization of urine beyond what occurs with U/d diet may or may not be necessary. The goal urine pH is neutral (7.0) and some owners may which 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 urinalysis will be periodically checked to see if any further steps in regard to urine pH control are needed.

After a month on this protocol, the stones are re-radiographed to compare their size to those on the original radiograph and a urinalysis is performed to assess pH. 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, surgery should be reconsidered. If surgery is still not an option, some other attempt at recovering stones should be made to check for the presence of xanthine stones (see below).

The disadvantages of stone removal by dissolution are:

  • It can take many months to dissolve uric acid bladder stones.
     
  • The protocol may not work.
     
  • The expense of radiographs 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 use of a urinary catheter to push the stone back into the bladder.

The average dog dissolves its stones in 3-4 months.

ALLOPURINOL: THE SHORT VERSION

Recall the original purine metabolism pathway:

Purines convert to Hypoxanthine which converts to Xanthine
which converts to Uric Acid which converts to Allantoin.

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!

Xanthine stones

If you know there will cheating on the diet, it is probably best not to use Allopurinol.

Allopurinol is dangerous in animals with poor kidney function.

Again, for more information about allopurinol, click here.

NOW THAT THE STONES ARE GONE: PREVENTION AND MONITORING

The diet of the stone-forming dog is the most important factor in preventing future stones episodes. Our goal is to feed a diet low in purines and create an alkaline urine (which is best to keep uric acid in solution). This is done by feeding a low salt, low purine diet such as Hills U/d, Hills K/d, Hills L/d, Hils D/d Egg and Rice formula (or other prescription low protein diet) or Royal Canin Urinary U/C.

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)
            Butter
            Cheese
            Eggs
            Fruits
            Milk

Allopurinol is generally required for prevention but at a lower dose than that required to actually 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 3-6 months thereafter. Imaging with ultrasound or with radiographs with contrast dye should be considered every 6 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. This test involves collecting all the urine a dog produces over either a 12 hour period and multiplying the value by two or actually collecting 24 hours of urine. This typically involves some kind of urine collection bag and a urinary catheter sewn in place (or a very very cooperative dog). It is very 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, 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 < 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 allopuriol and must be modified.

No one has formally tested the vegetarian diets for dogs to determine if they are adequately low in purines for stone prevention. Their use is a last resort for stone prevention (i.e. if the dog simply will not eat any of the appropriate foods.)

No one has formally studied the effect of joint nutriceuticals on urine pH. If one wants 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.

Page last updated: 3/2/2012