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Urate, Cystine, and Other Less Common Urinary Stones

Treatment and prevention of urate, cystine, xanthine, calcium phosphate, silica and compound uroliths.

Article by CJ Puotinen and Mary Straus, published in the Whole Dog Journal, June 2010

Photo of Gigi, Dalmatian with normal uric acid.

Also see these related articles:

Pictured is Gigi, one of the first two Dalmatians with a normal uric acid gene registered in Britain. See British Kennel Club Registers First LUA Dalmatian below for more information.


Introduction

Canine kidney and bladder stones may be painful and life-threatening, but an informed caregiver can help prevent them. By far the most common uroliths or stones in dogs are struvites (see Struvite Crystals and Stones) and calcium oxalate stones (see Calcium Oxalate Kidney and Bladder Stones). These two types represent about 80 percent of all canine uroliths.

Now we address the remaining stones that can affect our best friends: urate, cystine, calcium phosphate, silica, xanthine, and mixed or compound uroliths.

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Urate or purine stones

Of the remaining stone categories, urate or purine stones are the most common. They contain ammonium acid urate, sodium urate, or uric acid.

Only 6 to 8 percent of all uroliths are urate or purine stones, but their presence in certain breeds is significant. Dalmatians, English Bulldogs, Russian Black Terriers, Large Munsterlanders, Weimaraners, German Shepherd Dogs, Giant Schnauzers, American Staffordshire Terriers, Australian Shepherds, and South African Boerboels develop urates because of a genetic metabolic abnormality. Miniature Schnauzers and Yorkshire Terriers do so as a result of their tendency to have portosystemic shunts, which are abnormal blood vessels that bypass the liver, predisposing dogs to urate stones. These stones can form in dogs of any age, from very young puppies to seniors, but the most common age for forming urates is 1 to 4 years.

Of the breeds that develop urate stones, Dalmatians are most adversely affected. Between 1981 and 2000, the University of Minnesota College of Veterinary Medicine's Minnesota Urolith Center analyzed 7,560 stones from Dalmatians. Of these, 97 percent were from males and 95 percent were composed of urates. It's estimated that between 27 and 34 percent of male Dalmatians form urate stones, while the incidence in females is much lower.

It's tempting to assume that any stone a Dalmatian forms is a urate, but although 97 percent of stones from male Dalmatians were urate, they also included small percentages of struvite, xanthine, calcium oxalate, cystine, calcium phosphate, silica, and mixed or compound stones. The uroliths formed by female Dalmatians were 69 percent urate and 29 percent mixed or compound, with 2 percent struvite and 0.7 percent xanthine. Correct identification is a crucial first step in treating and preventing uroliths in all breeds, including Dalmatians.

The culprits in urate stone formation are purines, a type of organic base found in the nucleotides and nucleic acids of plant and animal tissue. As dietary purines degrade, they form uric acid, which is best known in human medicine for its connection to gout, a sharply painful form of arthritis. In susceptible dogs, purines trigger the formation of urate uroliths.

Urate stones are radiolucent -- that is, they cannot be identified in abdominal X-rays -- so their diagnosis is often made by the use of ultrasound, contrast dye X-rays, or analysis of urinary crystals or stones that were collected or removed.


Treating and preventing urate stones

The key to keeping urate-forming dogs healthy is to feed them a low-purine diet. Without the purines that trigger urate stone formation, even susceptible dogs can lead normal lives.

Some Dalmatian owners believe that giving their dogs who are prone to forming urate stone only mineral-free distilled water has helped prevent more stones from forming. No scientific evidence for this exists, however, and the quantity of water the dog consumes may be more important than its mineral content.

Because urate stones develop in acidic urine, an added prevention strategy is to feed foods that have an alkalizing effect. In general, meat is an acidifying food while most fruits and vegetables have an alkalizing effect. Vegetarian dog foods are sometimes recommended for this reason, but we consider vegetarian foods incomplete. Also, foods that use soy as a protein source are inappropriate for urate-forming dogs because soy is high in purines. However, soy-free vegetarian foods could be used as a base to which eggs, yogurt, cheese, and other low-purine protein sources are added. The same is true of some dog food pre-mixes, such as Sojo’s Grain Free Dog Food Mix. Sojo’s Complete is based on sweet potatoes, turkey, and eggs and might also be appropriate for dogs who are prone to forming stones. Avoid mixes that contain a lot of alfalfa, oats, or other foods that are high in purines (see Purine Content of Various Foods below).

Urate stones can be dissolved with a combination of a low-purine diet, urine alkalization, and control of secondary infections. The target range of urine pH during dissolution is 7.0 to 7.5. Care must be taken not to alkalize too much, making the urine pH higher than 7.5, because that can lead to the formation of calcium phosphate stones or shells around urate stones, making them difficult or impossible to dissolve.

The xanthine oxidase inhibitor allopurinol (brand name Zyloprim) may be prescribed short-term to reduce or inhibit the dog’s production of uric acid, which can help dissolve stones. This drug should not be used in patients with portosystemic shunts. A low-purine diet must be fed while giving allopurinol, as otherwise it predisposes dogs to the formation of xanthine stones and shells, making dissolution difficult. The long-term use of allopurinol as a preventative is not recommended but can be considered at low dosages when problems persist despite other treatment.

On average, it takes about 3½ months for stones to dissolve using allopurinol in combination with a low-purine diet and urinary alkalinization, but it can take as little as one month or as long as 18 months. As stones become smaller, they may move into the urethra and cause obstruction.

Some cases of severe kidney stones presumed to be ammonium urate resolved spontaneously following surgical shunt correction alone.


Monitoring urine pH

Urinary pH can be monitored using test strips with the goal of maintaining a neutral (7.0) pH in dogs prone to urate stones. Test strips can be held in the urine stream or urine can be collected in a paper cup, bowl, or other container for testing. Collecting the urine makes it possible to check for tiny stones or gritty “gravel” that the dog might be passing as well as any blood, pus, or other indications of infection. The recommended testing time is first thing in the morning, before feeding.

A change in urinary pH does not indicate the presence or absence of stones but does reveal conditions that are more or less likely to trigger stone production and will show the effect of dietary changes on the dog’s pH. A sudden jump in pH may signal a bacterial infection, which requires medical attention. It’s important to control urinary tract infections in dogs prone to forming stones.

If urine remains acidic and crystalluria (crystals in the urine) persists, alkalizing agents such as potassium citrate or sodium bicarbonate can be added.


Testing for hyperuricosuria

Hyperuricosuria is characterized by the excretion of uric acid leading to urate stone formation. After the defective gene that causes hyperuricosuria was discovered by researchers at the University of California, Davis, a test was developed to detect the mutation associated with the disease. This test is valid for all breeds.

Dogs affected by hyperuricosuria have two copies of the mutation, one inherited from each parent. Dogs with only one copy of the mutation are symptom-free carriers who pass the mutation on to an average of 50 percent of their offspring. Breeders can use DNA testing to identify carriers and effectively eradicate hyperuricosuria from their lines in breeds other than Dalmatians. (At present, all Dalmatians registered by the American Kennel Club in the United States are affected by the mutation. See LUA Dalmatians below.) When both dam and sire are clear of the mutation, all of their puppies will be clear as well.

The DNA test identifies dogs in three categories: clear of hyperuricosuria (the dog has two copies of the normal gene and no mutation), a carrier of hyperuricosuria (the dog has one copy of the normal gene and one of the mutation), or affected with hyperuricosuria (the dog has two copies of the mutation, causing high uric acid levels that can lead to urate stone disorders).

All dogs affected with hyperuricosuria are potential urate stone-formers. At any time, a combination of high-purine foods, insufficient fluids, insufficient opportunities to urinate, and overly acidic urine might cause the formation of urate uroliths. Periodic routine urinalysis to check for urate crystals can be used to monitor dogs with hyperuricosuria. The most accurate sample for this purpose is collected in the morning, assuming the dog has not urinated all night, so the urine is more concentrated. The sample should be collected in a clean glass, plastic, or other chemically inert container. To avoid false crystallization, the sample should not be refrigerated and should be tested within 30 minutes or as soon as possible.

While many Dalmatians never generate stones, it isn’t safe to assume that they can’t. In one widely reported case, a 13-year-old Dalmatian who had never shown symptoms began receiving two spoonfuls of a new supplement per day. Prior to this, his diet had been the same for all of his adult life. Within a few weeks, his urinary tract became completely obstructed by urate stones. While the supplement was low in protein (only 14 percent), its protein source was liver, a high-purine food.


The low-purine diet

Reducing purines in food is an effective way to reduce the risk of urate stones. Because most high-protein foods are also high in purines, veterinarians often recommend switching urate-forming dogs to a low-protein diet. However, it is not the quantity of protein that causes urate problems, it’s the type of protein. Dalmatians and other urate-prone dogs thrive on protein-rich diets that are low in purines, while these same dogs can develop stones after eating low-protein foods that contain even small amounts of  high-purine ingredients. Low-protein diets can lead to nutritional deficiencies when fed to adult dogs for long periods, and they are not appropriate for puppies and pregnant or nursing females at all. (See The Side Effects of Low-Protein Diets below.)

Because it’s difficult to find commercial pet foods that are low in purines without being nutritionally deficient, many owners of urate-forming dogs feed a home-prepared diet (see Homemade Diets for general information that can be modified using the information below).

Australian veterinarian Ian Billinghurst, whose book Give Your Dog a Bone introduced the BARF (Bones and Raw Food or Biologically Appropriate Raw Food) diet to dog lovers around the world, describes how to adapt his menus for urate-forming dogs in his report, Preventing Urate Stone Formation In Dalmatians Using A Basically BARF Diet:

“In Western countries today,” he says, “I am led to believe that a typical homemade diet for stone formers would contain about 80 percent rice, 10 percent vegetables, and 5 percent meat. This is an appalling diet to feed any dog. This is borne out by dogs forced to endure it. They suffer from numerous problems including continual hunger, a lack of energy, poor coat condition, and difficulty in maintaining weight or severe losses of weight.” Such a diet is not only deficient in protein, fat, vitamins, and minerals, he says, but it does not prevent stone formation.

The raw meaty bones Dr. Billinghurst recommends are chicken necks, chicken backs, chicken wings, and turkey necks. “Use plenty of puréed or pulped vegetables,” he says, “including lots of leafy greens. The diet could also include eggs, cottage or ricotta cheese, yogurt, and olive or flaxseed oil, supplemented with vitamin B complex, vitamin E, kelp, and a teaspoon of cod liver oil several times a week.” Cod liver oil is important for urate-forming dogs fed a homemade diet that does not include liver.

Feeding a changing variety of eggs, cheese, dairy products, and small amounts of medium-purine meat, poultry, and fish along with low-purine vegetables, fruits, and supplements – as well as ample water to keep urine diluted – can help any urate-forming dog stay healthy and happy. See Commercial Dog Food Makes Me BARF! for an example of a raw diet that worked for a confirmed stone-forming dog.

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Cystine stones

Photo of Mastiff, one of the breeds prone to cystinuria.

Cystine is a sulfur-containing amino acid essential to the health of skin, hair, bones, and connective tissue. Excess cystine is normally filtered by the kidneys so that it doesn’t enter the urine, but some dogs and humans are born with cystinuria, an inherited metabolic disorder that prevents this filtering action. When cystine passes into the urine, it can form crystals and uroliths.

Cystine stones are rare, representing 1 percent or less of uroliths identified in laboratories. Although any breed can develop cystinuria, certain breeds are most affected. An estimated 10 percent of male Mastiffs (pictured at right) have cystinuria. It is also common in Newfoundlands, English Bulldogs, Scottish Deerhounds, Dachshunds, Staffordshire Bull Terriers, and Chihuahuas. Cystine stones are faintly radiopaque, which makes them more difficult to see on X-rays than stones that contain calcium.

There are at least two types of cystinuria. The more severe form affects Newfoundlands and, rarely, Labrador Retrievers, and possibly some other breeds and mixes. In these dogs, males and females are equally affected (though as always, males are more likely to become obstructed). The age at onset can be as young as 6 months to 1 year. Recurrence of stones following surgery is more rapid in these dogs, and they are more likely to form kidney stones. The gene that causes cystinuria in these breeds has been identified and a simple, reliable genetic test can identify both affected dogs and carriers.

In other breeds, dogs with cystinuria are almost always male. No genetic test is available for them, though the University of Pennsylvania School of Veterinary Medicine (PennVet) is collecting blood samples from affected Mastiffs and their genetic relatives to try to produce a DNA test. The average age at onset of clinical signs is about 5 years.

A basic urinalysis can sometimes detect cystine in urine, though this is the least reliable method of detection. A nitroprusside (NP) test performed at the University of Pennsylvania (PennGen) is considered more reliable. A quantitative amino acid analysis performed by PennGen or a human medical laboratory is most reliable but very expensive. If cystine is found in the urine on any of these tests, the diagnosis is considered positive for cystinuria, though that doesn’t necessarily mean the dog will form stones. Unfortunately, a negative result on any of these tests does not guarantee that the dog is “clear.” Note that sulfa drugs and supplements, including sulfa antibiotics, MSM and Deramaxx, may cause false positive results.

“Cystinuria is a particularly frustrating condition to manage,” says San Francisco Chronicle pet columnist Christie Keith, who started a Canine Cystinuria e-mail list and website when one of her Scottish Deerhounds developed cystine uroliths. “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.”

Cystine, like all amino acids, is one of the building blocks of protein. That's why most veterinarians (including many kidney specialists) prescribe a low-protein diet, speculating that reducing cystine supply will reduce the formation of cystine stones. Another common recommendation is to alkalize the dog’s urine because cystine stones form in acid urine.

Unfortunately, says Keith, these strategies are ineffective. “Most of us on the Canine Cystinuria list have found that diet and urinary alkalization have failed to prevent our dogs from forming stones,” she says, “and they have sometimes caused other problems, including other types of stones that form in alkaline urine. If the urine goes into acidity even briefly, cystine stones can form and they won’t dissolve just because alkaline urine is achieved soon after. In addition, feeding ultra-low-protein diets can be dangerous, especially to giant breeds and breeds prone to cardiomyopathy.” (SeeThe Side Effects of Low-Protein Diets below.)

It’s important to provide your dog with extra fluids and frequent opportunities to urinate in order to keep his urine from becoming supersaturated. Salt should not be added to increase fluid consumption for dogs with cystinuria; according to studies conducted on humans, a low-sodium diet may decrease the amount of cystine in the urine.

If urine alkalization is attempted, the target pH is 7.0 to 7.5; higher can predispose dogs to calcium phosphate uroliths. Potassium citrate is preferred for alkalization when needed rather than sodium bicarbonate because sodium may enhance cystinuria.

Cystine stones cannot be dissolved with diet or supplements, but two prescription drugs can help dissolve and prevent them. Cuprimine (d-penicillamine) has potentially serious side effects but is less expensive and more readily available, and many dogs do well on it. According to Keith, Thiola (tiopronin, also referred to as 2-mercaptopropionylglycine or 2-MPG), has fewer side effects, but one of them is the depletion of the owner’s bank account. Maintaining a giant-breed dog on Thiola can cost as much as $500 per month. Because the severity of cystinuria tends to decline with age, the dosage of preventative medications can sometimes be decreased or even stopped.

Dissolution requires a combination of medication, low-protein diet, and urinary alkalinization. Even then it may not be successful or practical for a dog with numerous stones. When it does work, dissolution commonly takes one to three months.

For some dogs, the solution has come not from prevention strategies or medication but from surgery. “It sounds extreme,” says Keith, “but many of us who have stone-forming male dogs with cystinuria have opted for a scrotal urethrostomy. This surgery redirects the dog’s urethra away from the penis to a new, surgically created opening in front of the scrotum.”

The wider opening that results enables males to more easily pass small stones and helps to prevent urinary blockages. “While future obstruction is not impossible,” says Keith, “this procedure reduces the risk substantially.” Still, she cautions, this surgery should not be undertaken lightly. It’s expensive, requiring the expertise of a skilled board-certified surgeon, and because the affected area is rich in blood vessels, there can be significant post-surgical bleeding, though the surgery is not particularly painful.

“The good news,” she says, “is that many dogs, including stone-formers and those who had serious complications when their condition was first diagnosed, have lived not just normal but longer-than-normal lives.”

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The remaining three

Like cystine stones, stones composed of xanthine, calcium phosphate, and silica are rare, each representing less than 1 percent of analyzed uroliths. Ironically, they often occur while the patient is undergoing treatment for the prevention of other stones.

Although xanthine is a type of purine, xanthine stones are associated not with diet but with the use of allopurinol, the drug used to treat urate stones as well as canine leishmaniasis. Xanthine crystals almost never occur naturally, though they have been reported in some cats, Cavalier King Charles Spaniels, and Dachshunds. The average age at onset is 6 to 7 years. Like urate stones, they are radiolucent; that is, they cannot be seen on X-rays.

In some cases, discontinuing allopurinol while feeding a low-purine diet has dissolved xanthine uroliths, but in general, treatment consists of surgical removal, urohydropropulsion (a nonsurgical procedure performed with the dog under anesthetic, in which the bladder is filled with saline through a catheter, and the bladder is manually squeezed to force stones out through the urethra), or lithotripsy (the use of high-energy sound waves to break up the stones).

A low-protein diet is usually recommended for dogs receiving allopurinol treatment (to help prevent the formation of xanthine uroliths), but once again what's really needed is a low-purine diet, not restricted protein.


Calcium phosphate stones often develop when the urine is over-alkalized (at a pH greater than 7.5), in an effort to prevent the formation of calcium oxalate, urate, or cystine stones. The average age at onset is 7 to 8 years, but these stones have been found in dogs of all ages, including puppies and seniors.

Calcium phosphate stones are commonly called apatite uroliths, with hydroxyapatite and carbonate apatite the most common. They are radiographically dense, so they are easily seen on X-rays. Uroliths composed primarily of calcium phosphate are rare and associated with metabolic disorders such as hyperadrenocorticism (Cushing’s disease), hypercalcemia, renal tubular acidosis, or excessive calcium and phosphorus in the diet.

Because they cannot be dissolved medically, these stones are usually removed surgically, though that may be unnecessary if the stones are clinically inactive (not growing or causing problems). They have been known to dissolve spontaneously following parathyroidectomy surgery for primary hyperparathyroidism. Unless the patient has a metabolic condition that contributes to calcium phosphate stones, the strategies used for prevention are similar to those used for calcium oxalate stones, although it’s important to avoid excessive alkalization of the urine.

Medications that can enhance calcium excretion, including prednisone and furosemide (Lasix), should be avoided if possible. Salt should not be added to the diet, as sodium increases urinary calcium.


Silica stones are most common in male German Shepherds, Old English Sheepdogs, Golden Retrievers, and Labrador Retrievers, although other breeds and mixed breed dogs have developed them as well. More than 95 percent of silica stones occur in males. The problem can develop in dogs as young as four months or as old as 12 years, but most stones occur in dogs aged 6 to 9 years. Silica stones are radiopaque and can be seen on X-rays. No relationship has been found between urinary pH and silicate urolith formation.

The formation of silica stones is associated with diets high in cereal grains, particularly corn gluten and soy bean hulls, both of which are high in silicates. Corn gluten and soy bean hulls (also called soybean mill run) are ingredients in low-quality prescription diets and dog foods.

Other foods that are high in silica, and which should be avoided, include the hulls of wheat, oats, and rice (hulls are found in whole grains); sugar beets; sugar cane pulp; seafood; potatoes and other root vegetables; onions (which shouldn’t be fed to dogs, anyway); bell peppers; asparagus; cabbage; carrots; apples; oranges; cherries; nuts and seeds; grains; soybeans; and the herbs alfalfa, horsetail, comfrey, dandelion, and nettles. Most of the carbohydrated used in grain-free dry foods, including peas and tapioca, appear to be high in silica. Bentonite clay, a mineral supplement, is also high in silicates.

Because no drug or diet dissolves silica stones, they may be removed surgically, flushed out with urohydropropulsion, or shattered with lithotripsy; no treatment may be required for clinically inactive stones. Silica stones do not usually recur, but it makes sense to feed a diet that is high in protein from animal sources and low in plant foods, including fiber and bran. Canned foods are often higher in protein and lower in plant foods than dry kibble. Some frozen raw and cooked foods do not include vegetables or grains.

As with all stones, keep the urine diluted by increasing fluids and giving the dog frequent opportunities to urinate. Don’t add salt, which is another source of silica.

Dogs who drink water from sources containing sand may develop silica uroliths, so water that contains silica (a primary mineral in sand) should be avoided. In hard-water areas, distilled water is recommended for dogs who form silica stones. Silica stones have also been associated with pica, an eating disorder that causes dogs to eat dirt, rocks, and other non-food items.

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Mixed and compound uroliths

Most bladder stones are caused by a single type of mineral. Sometimes a stone consists of two or more minerals in approximately equal proportions, in which case it is called a mixed urolith. These stones are rare, comprising only 2 percent of analyzed uroliths.

A stone that consists of a core mineral surrounded by a smaller amount of a different mineral is called a compound urolith. These make up 10 to 12 percent of analyzed stones. Compound uroliths can sometimes be identified based on differing radiographic density of their stone layers.

Compound uroliths develop when a stone’s environment changes, such as when a struvite stone is treated by reducing urinary pH, magnesium, and phosphorus, resulting in a calcium oxalate shell around the struvite core. Struvite shells caused by infection commonly form over calcium oxalate and other cores, especially since all stones predispose dogs to bladder infections.

One treatment strategy is to try to dissolve the outer layer first. This is especially effective for stones with an infection-induced struvite shell, which make up more than 80 percent of compound uroliths with cores other than struvite. The struvite shell should dissolve with appropriate antibiotic or infection-fighting treatment. X-rays can be used to monitor dissolution. Once the outer shell disappears, treatment strategy switches to the inner core, also called the nucleus, or the stones may then be small enough to remove by urohydropropulsion.

More than half of the compound uroliths analyzed in 2002 by the Minnesota Urolith Center contained a calcium oxalate core, and almost all of these were surrounded by a struvite shell caused by infection. Unlike calcium oxalate uroliths, these compound uroliths were found primarily in female dogs; this is because the female dogs’ anatomy makes them more susceptible to urinary tract infections, which cause struvite stones. Treatment and prevention should be focused on controlling infections and reducing the risk of calcium oxalate stones (see Calcium Oxalate Kidney and Bladder Stones).

Stones with a struvite core made up almost a quarter of compound uroliths, more than half of which were surrounded by a calcium phosphate shell and most of the rest by a calcium oxalate shell. As is common with infection-induced stones, most of these dogs were female.

Urinary acidifiers can contribute to urinary calcium that leads to the formation of calcium-containing stones. Treatment is the same as for struvites: appropriate medication for the infection and possibly a reduced-protein diet short-term to help dissolve the stones quickly. Urinary acidification is not recommended due to the increased risk of calcium oxalate and calcium phosphate formation.

Small percentages (3 to 5 percent each) of compound uroliths were comprised of the following:

Sulfa drugs may create a shell around struvite uroliths when used at high doses for prolonged periods, or in dogs with acidic or highly concentrated urine. For this reason, sulfa drugs should be avoided when treating lower urinary tract (bladder) infections, particularly for dogs known to have stones or one of these risk factors.

Preventive treatment should focus on whatever minerals comprised the stone’s inner core. As with all types of stones, increasing fluid intake and opportunities to urinate are recommended. Adding salt to the diet is not recommended, however, as it increases urinary calcium and calcium is commonly found in uroliths.

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Preventing recurrence

Once your dog’s stones are successfully treated, you’ll want to use the strategies described here to help keep them from coming back. Stone-forming dogs can be monitored by their veterinarians with X-rays, ultrasound, and urinalyses.

Infection-induced struvites can recur in as little as a few days to a few weeks, while calcium oxalate and silica stones may take a few months to recur. Cystine and urate stones can recur rapidly.

Some dogs continue to form stones despite diet changes and medical therapy. For them the key is monitoring with radiographic imaging (X-rays or ultrasound) at least every 3 to 6 months (more often to start with and for rapidly recurring types) in order to detect stones while they are still small enough to pass through the urethra using urohydropropulsion or catheter-assisted retrieval.

A final solution for males with recurring stone blockages is urethrostomy surgery, which redirects the flow of urine to avoid its normal narrow passage.

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