Stalking stones: An overview of canine and feline urolithiasis

Urolithiasis is common in dogs and cats, causing morbidity and, occasionally, mortality. Although renal and ureteral uroliths can sometimes be more difficult to manage, uroliths can usually be successfully treated medically or surgically or by performing lithotripsy. Long-term success is possible. This article will help you diagnose urolithiasis, determine the urolith composition, and develop an appropriate treatment and prevention plan.

CLINICAL SIGNS

Uroliths in small animals occur most frequently in the bladder (urocystolith) but can also be found in the urethra (urethrolith), ureters (ureterolith), and kidneys (nephrolith). Clinical signs of urolithiasis vary according to the urolith's location and any underlying or predisposing conditions. In addition, some uroliths do not produce clinical signs and may be discovered incidentally.

Since the bladder is the most common site for uroliths, the most frequent clinical signs observed are dysuria, hematuria, and pollakiuria with or without inappropriate urination.

If the urethra contains uroliths, the same signs may be observed, with the possible addition of blood dripping from the prepuce or vulva independent of urination. Urethral obstruction may result in unsuccessful micturition attempts, lethargy, anorexia, vomiting, abdominal distention, or pain.

Ureteroliths and nephroliths may be associated with hematuria and abdominal pain as well as lethargy, fever, decreased appetite, and vomiting if an upper urinary tract infection or obstruction is involved.

DIAGNOSIS OVERVIEW

Urolithiasis diagnosis may be aided by historical information, such as a previous occurrence of urolithiasis or an owner's observation of signs compatible with uroliths. A predisposition to urolithiasis may be indicated by patient signalment or pre-existing medical conditions favoring urolith formation. Routine laboratory test (complete blood count, serum chemistry profile, urinalysis) results do not specifically detect uroliths but provide valuable information about predisposing or complicating medical conditions.

Urinalysis

Urinalysis findings, including the pH, evidence of bacterial infection, and the presence of specific crystal types may indicate urolith composition. Urinalysis is best performed within 30 minutes of sample collection. Refrigeration helps preserve the urine sample but can alter the chemical and sediment findings. In particular, time and refrigeration lead to pH and temperature changes, which enhance crystal formation and cause misinterpretation of the urinalysis results.1

Physical examination

You may identify a firm object in the bladder during abdominal palpation or find very small uroliths in voided urine or in penile or vulvar mucoid discharge. Rectal examination findings may reveal firm objects in the pelvic urethra.

Imaging

In most cases, definitively diagnosing urolithiasis requires ultrasonography, survey abdominal or urethral radiography, or contrast radiography. Obtain survey images of the entire length of the urinary tract to identify whether uroliths are present in multiple locations and to identify any factors predisposing the patient to urolith formation, such as infection or neoplasia. Determining the exact number of uroliths with any of the imaging modalities can be challenging in some cases.

Ultrasonography is a good initial imaging tool to detect uroliths; however, it does not reveal the radiodensity or shape of uroliths. In addition, unless a patient's size allows for the use of a rectal transducer, the pelvic urethra cannot be seen with ultrasonography.

Survey radiography can reveal the radiodensity and approximate size and contour of uroliths. It is also generally the most cost-effective and available noninvasive procedure for initially evaluating uroliths.

Although high-frequency (5 to 7.5 MHz) ultrasonography compared favorably with double-contrast cystography in detecting urocystoliths and determining urolith numbers in one study, double-contrast cystography has the added benefit of being a sensitive and specific indicator of urolith shape and size.2,3

When imaging patients with confirmed urolithiasis or with clinical signs suggestive of urolithiasis, include as much of the urethra as possible since uroliths could be missed (Figures 1A & 1B). Position identification labels and other imaging markers so they do not obscure any part of the urinary tract (Figure 1B).

Figure 1A. A lateral abdominal radiograph of a dog examined for the primary complaints of hematuria and dysuria. No uroliths are observed in the urinary tract, including the portion of the urethra that can be seen on the film.

If initial imaging results do not reveal an obvious cause of the patient's clinical signs or are inconclusive, attempt urethral catheterization and perform a retrograde contrast study if necessary. Also, perform a rectal examination to palpate the urethra and rule out other concomitant disorders, such as prostatic disease or urethral neoplasia.

Figure 1B. A lateral radiograph of the dog from Figure 1A showing the proper positioning of a patient to view the length of the urethra, including the perineal and penile urethra. Note the four radiopaque urethroliths proximal to the os penis (straight arrow). The identification label on the film (curved arrow) may be obscuring a portion of the urethra.

When catheterizing a patient's urethra, you may note a grating sensation as the catheter moves past small uroliths, or the uroliths may prevent catheter passage. Resistance to catheterization is normal at the base of the os penis and pelvic flexure in male dogs. Successfully catheterizing a male cat typically requires sedation or anesthesia and appropriate extension of the penis away from the patient's body (Figure 2). Occasionally, a urinary catheter may pass by uroliths without indicating their presence, especially when you use a relatively small diameter catheter.

Figure 2. Extending the penis and prepuce away from the body of a sedated or anesthetized cat will facilitate transurethral passage of a urinary catheter.

Ruling out urethroliths and, in some cases, urocystoliths may require performing retrograde cystography or urethrography. This imaging technique may also be indicated to help establish the exact location and approximate number of uroliths (Figure 3).

Figure 3. Retrograde positive contrast study in the patient from Figure 1A. Note the filling defects in the urethra where the four uroliths (arrow) seen in Figure 1B are located.

TREATMENT OVERVIEW

If the patient is stable, take steps to determine the likely urolith composition and to develop a treatment plan. If the patient is relatively asymptomatic, monitoring the pet's condition and establishing measures to prevent further urolith formation may be all that is needed.

Relieve urethral obstruction

If the patient is not stable or has a complicating condition or a urethral obstruction, stabilize the patient and resolve the obstruction. Techniques for propulsing urethral uroliths or plugs (macroscopic aggregate of organic matrix and crystals) retrograde into the bladder or antegrade through the urethral orifice are discussed in the boxed text titled "Antegrade and retrograde urethral urohydropropulsion in male dogs or cats."

Antegrade and retrograde urethral urohydropropulsion in male dogs or cats

If a urethral obstruction cannot be safely resolved in a timely manner, perform cystocentesis to decompress the bladder or place a cystostomy tube to allow a temporary outlet for urine until the obstruction can be eliminated. If the patient is at high risk for reobstruction, has had excessive trauma to the urethra in the process of relieving the obstruction, or has developed an atonic bladder due to prolonged obstruction, place an indwelling urinary catheter with a closed collection system. (See the boxed text titled "Placing an indwelling catheter and a connection to a closed urine collection system.") Avoid placing indwelling urinary catheters indiscriminately because of the increased risk of associated bacterial infection.

Placing an indwelling catheter and a connection to a closed urine collection system

Nonobstructed patients

Uroliths can be eliminated in patients without a urethral obstruction by voiding urohydropropulsion (see the boxed text titled "Voiding urohydropropulsion in dogs and cats") surgical removal, lithotripsy, medical dissolution, or new minimally invasive interventional radiographic and endoscopic techniques.

Voiding urohydropropulsion in dogs and cats

Voiding urohydropropulsion. Urethral size is a limiting factor for voiding urohydropropulsion; a male cat with urocystoliths > 1 mm in diameter is not a candidate for this procedure unless the cat has undergone perineal urethrostomy.4,5 Voiding urohydropropulsion is also a poor choice for patients with a urethral obstruction, a history of recent urinary bladder surgery, or an unresolved urinary tract infection.6

Surgery. Depending on the location of the uroliths, surgical intervention, such as removing uroliths through an incision into the kidney, ureter, bladder, or urethra or, occasionally, removing a severely affected kidney or ureter, may be indicated. Radiographic or ultrasonographic imaging is always recommended after surgically removing uroliths to make sure no uroliths remain.7

Lithotripsy. Lithotripsy can be accomplished by intracorporeal electrohydraulic, laser, or ultrasonic techniques or by an extracorporeal shock wave method. Intracorporeal electrohydraulic lithotripsy breaks up uroliths by using repetitive shock waves conducted through a flexible probe placed endoscopically next to the targeted urolith. Laser lithotripsy uses light-amplified thermal energy to fragment uroliths through fibers endoscopically positioned adjacent to the selected urolith.8 Ultrasonic lithotripsy uses high-frequency sound waves delivered to the urolith through an endoscopically placed electronic probe. Extracorporeal shock wave lithotripsy breaks up uroliths through focused shock waves generated from equipment positioned outside the patient's body.

The urolith fragments produced through lithotripsy must be small enough for the patient to eliminate them through voided urine, or they must be extracted by using suction devices or grasping instruments. The use of lithotripsy is limited by a patient's size and sex, the availability of the specialized equipment, and the size, number, and composition of uroliths involved.

Traditionally, intracorporeal electrohydraulic lithotripsy techniques involve transurethral passage of equipment, making these methods best-suited for fragmenting cystoliths and urethroliths in female dogs and cats, male dogs weighing > 11 lb (5 kg),9 and male cats that have had a perineal urethrostomy performed. Extracorporeal shock wave lithotripsy has been used primarily for fragmenting nephroliths and ureteroliths in dogs only. Although laser lithotripsy use is becoming more widespread, most of these techniques are limited to a small number of institutions and large, private referral practices.

Medical dissolution. Medical dissolution through a special diet can be used as a primary means of urolith elimination or as a secondary procedure after urolith removal by other methods to ensure that all uroliths or fragments have been eradicated. When used as a primary method of urolith elimination, medical dissolution techniques generally require feeding only the prescribed diet for one month beyond radiographic or ultrasonographic evidence of urolith dissolution. Complications from obstruction and the lack of consistent exposure to urine altered by diet and medication make dissolution protocols unlikely to be effective for treating uroliths located in the ureter or urethra.10 Medical dissolution protocols are discussed in "Specific urolith characteristics, treatments, and prevention."

Increase water intake

Increasing the water intake in dogs and cats is an important part of treating and preventing uroliths. Feeding a patient a canned diet or adding water to dry food increases urine volume, decreases the concentration of urine minerals potentially involved in urolith formation, and helps eliminate these minerals through more frequent urination.11,12 Successful dilution can be evaluated by periodically checking a patient's urine specific gravity to see if it remains < 1.020.13-15

Consider new minimally invasive methods

New techniques combining interventional radiographic and endoscopic procedures have enhanced the diagnosis and removal of uroliths.16,17 Fluoroscopy, ultrasonography, and endoscopy are used to identify and retrieve uroliths located virtually anywhere in the urinary tract. This combination of methods can be used to place stents to relieve urolith-related obstruction and to facilitate antegrade passage of uroliths. The development of percutaneous approaches has improved accessibility to sites such as the renal pelvis (percutaneous nephrolithotomy), allowing ultrasonic and laser lithotripsy to be performed with less damage to the surrounding tissues. Although most of these techniques have limited availability at veterinary facilities, continued success in treating uroliths with these minimally invasive methods should increase their availability to veterinary patients in the coming years.

Identify urolith composition and bacteria

Because urolith composition is an important factor in determining the treatment and prevention options, it is important to accurately identify urolith composition whenever possible. The most direct method of determining urolith composition is analyzing the urolith itself. Uroliths can be collected for submission through surgical intervention, routine voiding, voiding urohydropropulsion, or catheter-assisted retrieval. (For more information on this technique, see the boxed text titled "Catheter-assisted urolith retrieval.")

Catheter-assisted urolith retrieval

Analysis can be either qualitative or quantitative. Qualitative analysis is performed by several laboratories and can determine the approximate urolith composition. Quantitative analysis uses more sophisticated techniques to determine the exact composition of the urolith's nidus (nucleus), body, and shell, including the exact percentages of mixed components. Quantitative analysis is the preferred method for determining urolith composition because it provides a much more accurate analysis when compared with qualitative methods and greater guidance in developing appropriate therapeutic and preventive plans.18

For best results, submit the entire urolith in a dry, unbreakable container. If the patient has multiple uroliths, submit either all the uroliths recovered or a representative assortment for quantitative analysis. Urolith fragments may be collected for quantitative analysis after lithotripsy by using stone baskets or grasping instruments at the time of the procedure or by collecting voided urine after the procedure and pouring it through a tea strainer.

The Minnesota Urolith Center at the University of Minnesota College of Veterinary Medicine will perform quantitative analysis of uroliths at no charge except for standard shipping fees. Submission forms and information can be obtained at http://www.cvm.umn.edu/depts/minnesotaurolithcenter/howtosubmitsamples/home.html. Quantitative analysis can also be performed for a fee at the Urinary Stone Analysis Laboratory at the University of California at Davis School of Veterinary Medicine or at human laboratories such as the Urolithiasis Laboratory at the Baylor College of Medicine in Houston or the Louis C. Herring and Company laboratory in Orlando, Fla.

Submitting or saving a recovered urolith, including the nidus, for bacterial culture is recommended in cases in which results of a urine culture are negative or pending, especially in dogs suspected of having struvite uroliths. Submit an entire urolith for bacterial culture in a dry, clean container. Refrigeration is not required for storage or shipping, but, as with all cultures, the specimen should be cultured as soon as possible for optimal results. Antibiotic treatment initiated before urolith recovery may infrequently cause the shell surface and the patient's urine to be sterile; however, viable bacteria may still be present in the urolith's center.10 Although bacteria do not always play a primary role in urolith formation, bacterial infection often accompanies uroliths and represents a complicating factor in treatment.

Often a urolith is not readily available for direct analysis. In those cases, using the patient's signalment to establish any potential breed, age, or sex predisposition together with radiographic examination findings, bacterial culture, and urinalysis results from a fresh, nonrefrigerated sample can provide valuable information regarding potential urolith composition. For example, isolating urease-producing bacteria from the urine is a strong indication of struvite composition, particularly in dogs.

Although identifying specific urine crystals may help determine the urolith composition, several factors must be kept in mind when evaluating the importance of crystals. Many of the commonly recognized crystals can be considered normal findings in urine samples. Their presence does not necessarily indicate that urolith formation will follow or that the composition of any given urolith will match the crystal type identified. In addition, uroliths can be found in some patients that have no identifiable urine crystals. Treatment and prevention plans should always be in response to actual urolith or plug formation and not in response to the presence of crystals alone.

SPECIFIC UROLITH CHARACTERISTICS, TREATMENTS, AND PREVENTION

The following discussion focuses on the characteristics of specific therapeutic and prevention options. Table 1 lists many of the diet options for the dissolution and prevention of canine and feline uroliths. The entries are based primarily on the manufacturer's diet formulation descriptions for nutritionally managing animals with particular crystal and urolith compositions. Few studies are published in peer-reviewed journals that evaluate the efficacy of specific diet formulations in dogs or cats with naturally occurring uroliths.19,20 Table 2 is a quick reference for urolith diagnosis, treatment, and prevention recommendations.

Table 1. Selected Canine and Feline Diets That May Be Used in Urolith and Crystal Dissolution and Prevention Protocols

Struvite

Struvite (magnesium ammonium phosphate hexahydrate) uroliths are one of the most common uroliths in dogs and cats. Although struvite was the most prevalent urolith composition overall in dogs from 1981 to 2005 (43.5%) according to one study,21 the occurrence of struvite uroliths in dogs steadily declined during that same period and struvite became the second most prevalent urolith composition in dogs beginning in 2004 (39%).21

Table 2. Quick Reference Guide for Uroliths in Dogs and Cats

A study at the Minnesota Urolith Center analyzing uroliths in cats from 1981 to 2002 also revealed a change in struvite urolith prevalence.22 In 1981, struvite uroliths represented most uroliths in cats (78%), but a steady decline was seen over several years, with struvite decreasing to an overall prevalence of about 33% from 1994 to 2002. Beginning in 2003, the frequency of struvite uroliths in cats began to notably increase, reaching 48.1% in 2005 and again establishing struvite as the most prevalent urolith composition identified in cats at the Minnesota Urolith Center.22 A separate California study analyzing a large number of uroliths in cats over a similar period supports the trend in recent increases in struvite uroliths.23

The shifts in urolith frequency in both dogs and cats have been theorized to be the result of commercial maintenance diet reformulation and the increased use of therapeutic diets designed to dissolve or prevent uroliths.22,23 However, this theory does not seem to explain the fact that during the same 25-year period, the mineral composition of urethral plugs in cats has remained consistently and primarily struvite (87% in 2005).22

Characteristics. Struvite uroliths vary greatly in size, ranging from sandlike particles to specimens more than 1 cm in diameter. They are generally sufficiently radiopaque to be seen easily on survey films. These uroliths assume a variety of shapes but are often spherical or pyramidal (flat-sided). Uroliths that are pyramidal or > 1 cm in diameter are most often of struvite origin.14,24,25 In some cases, a struvite urolith will take on the shape of the urinary tract surrounding it (Figures 4A-4C). Struvite crystals more readily precipitate in alkaline urine and have an angular, prismlike appearance.

Figure 4A. A ventrodorsal abdominal radiograph of a 7-year-old, castrated male basset hound reveals a large radiopaque nephrolith conforming to the shape of the left renal pelvis.

Struvite uroliths can be either sterile or bacterial in origin. Infection-related uroliths occur more commonly in dogs between 2 and 9 years old and in cats < 1 year old and > 10 years old.13,14,24,25 Most struvite uroliths in dogs are caused by a urinary tract infection, occur predominantly in females, and have a breed predisposition for miniature schnauzers, Shih Tzus, bichon frises, miniature poodles, cocker spaniels, and Lhasa apsos.24 Most struvite uroliths in cats are sterile and not associated with a known sex predisposition. Cat breeds predisposed to struvite formation include the foreign shorthair, Ragdoll, Chartreux, Oriental shorthair, domestic shorthaired cat, and Himalayan.25 The age predisposition for sterile struvite urolith formation in cats is between 1 and 10 years old with the incidence decreasing after about 7 years of age.

Figure 4B. The same nephrolith seen in Figure 4A as seen during the nephrogram stage of an excretory urogram. Note the remnant of the left renal pelvis seen as a dark zone adjacent to the nephrolith.

Sterile struvite uroliths may be associated with increased to normal magnesium concentrations in the diet, but it is still unclear whether magnesium triggers struvite urolith formation.13,14 Alkaluria and low urine volume also appear to put cats at risk for developing sterile struvite uroliths.

Figure 4C. The same nephrolith seen in Figures 4A and 4B, exposed after nephrectomy. The composition of the body of the nephrolith was 95% magnesium ammonium phosphate hexahydrate and 5% calcium phosphate and of the shell was 80% magnesium ammonium phosphate hexahydrate and 20% calcium phosphate.

Infection-related struvite uroliths occur as a result of an underlying urinary tract infection. The bacteria involved are most commonly urease-producing Staphylococcus species, although urease-producing Proteus species and, rarely, ureaplasma organisms may also be involved.24 Occasionally, other bacteria are cultured from affected patients. The breakdown of urea by the bacteria releases ammonia into the urine, increasing the pH and availability of ammonium and phosphate ions, all of which predispose a patient to struvite urolith formation.

Treatment. Feeding a calculolytic diet (Table 1) can dissolve both sterile and infection-related struvite urocystoliths and nephroliths by creating an acidic, dilute urine undersaturated with magnesium, ammonium, and phosphorus.24-27 The dissolution time for uroliths varies, but it averages about two to three months for infection-related uroliths and three to six weeks for sterile uroliths.24-26 Dissolution of infection-related struvite uroliths occurs more rapidly if an appropriate antibiotic is administered concurrently. Antibiotic therapy is best determined by bacterial culture and antimicrobial sensitivity testing of urine obtained by cystocentesis. Ideally, a urine culture should be performed before antibiotics are initiated and periodically during the dissolution process.

By evaluating serial urinalyses and abdominal radiography or ultrasonography every four weeks, dissolution therapy can be altered as needed for individual patients. Urinalysis findings compatible with an ongoing infection (bacteriuria, pyuria, alkaluria) indicate a need to reassess antibiotic therapy through urine bacterial culture and antimicrobial sensitivity testing. Diagnostic imaging is the primary means of determining the success of the dissolution therapy. Continue the calculolytic diet and antibiotic administration for one month after complete dissolution of uroliths as established by imaging.19,24,25

A calculolytic diet is not a maintenance diet. For example, according to the manufacturer's product guide (2005 Hill's Key to Clinical Nutrition), Prescription Diet s/d feline and canine (Hill's Pet Nutrition) should not be fed for longer than six months. The nutrient restrictions, fat content, and increased sodium content of s/d make it unsuitable as a diet for puppies or kittens, pregnant or lactating pets, and pets with heart failure, hypertension, or renal failure.

In a recent study in which the results are unpublished, an alternative protocol for treating infection-related struvite urocystoliths in a small number of dogs has preliminarily shown dissolution of these uroliths by feeding a maintenance, noncalculolytic diet (e.g. Science Diet Adult Original [Hill's Pet Nutrition], Dog Chow [Purina]) combined with antibiotic therapy and the urinary acidifier d,l-methionine (Methio-Form—Vet-A-Mix; 100 mg/kg orally twice a day).26 This alternative protocol is still under evaluation but could be considered for treating struvite urocystoliths in dogs that refuse to eat the specially formulated calculolytic diets.

Failure to dissolve struvite uroliths with an appropriate therapeutic regimen and owner compliance may indicate that the targeted uroliths are not composed of struvite or have layers containing greater than 20% nonstruvite minerals.24,28 Calcium phosphate and calcium carbonate phosphate are occasionally associated with struvite uroliths and may interfere with medical dissolution therapy.

Not all patients with suspected or confirmed struvite uroliths are candidates for medical dissolution because of noncompliant owners, complicating health circumstances (e.g. hypertension), or ureteral or urethral uroliths. Surgical removal, lithotripsy, or voiding urohydropropulsion should be considered in these patients depending on the circumstances.

Prevention. Prevent sterile struvite uroliths by having owners feed their pets one of the many available diets that increase urine volume, decrease urine pH to < 6.8, and decrease excretion of magnesium, ammonium, and phosphorus (Table 1). In struvite prevention programs in which patient obesity is a concern, canine and feline Prescription Diet w/d (Hill's Pet Nutrition) can be used. Preventive diets for sterile struvite uroliths are less restrictive than the calculolytic diets but should not be given to puppies or kittens, pregnant or lactating patients, or dogs at risk for pancreatitis.

Although these diets can be fed to patients with infection-related struvite uroliths, special dietary management is not specifically indicated. The key to preventing these uroliths is to eradicate the bacterial infection and periodically monitor for infection recurrence with urinalyses and bacterial cultures.26

Calcium oxalate

Calcium oxalate uroliths have had an inverse relationship with struvite uroliths over the last several years in both dogs and cats.21,23 In dogs, as the incidence of struvite uroliths has gradually decreased, the incidence of canine calcium oxalate uroliths has steadily increased, surpassing struvite in frequency of occurrence.21 The incidence of struvite and calcium oxalate uroliths in cats has followed a similar course except for the last few years, which have seen a decline in the incidence of calcium oxalate and an increase in struvite uroliths. In 2005, the Minnesota Urolith Center reported calcium oxalate was the second most frequent type of urolith in cats.22

Characteristics. Calcium oxalate urolith formation has been reported to have a male predisposition in both cats and dogs.14,23 Small-breed dogs are predisposed, including miniature schnauzers, Lhasa apsos, Yorkshire terriers, bichon frises, Shih Tzus, and miniature poodles.29 Dogs 8 to 12 years old and older cats (bimodal peaks at 5 and 12 years of age) have the greatest risk of developing calcium oxalate uroliths.14,23 Cat breeds predisposed to calcium oxalate formation include Ragdolls, British shorthairs, foreign shorthairs, Himalayans, Havana browns, Scottish folds, Persians, and exotic shorthairs.25 Cats housed indoors may also be at a greater risk for developing calcium oxalate uroliths, which could be a result of a decrease in water consumption and voiding.30

Calcium oxalate uroliths are radiopaque and are usually readily seen on survey radiographs. This urolith type varies in size and shape, taking on a smooth appearance or jagged rose rock appearance. Calcium oxalate uroliths are made up of two different types of crystals, monohydrate and dihydrate. Calcium oxalate uroliths composed predominantly of monohydrate crystals, which appear in the shape of a dumbbell or have a picket-fence shape microscopically, usually have a smoother contour grossly than do uroliths composed predominantly of dihydrate crystals, which have a classic Maltese-cross appearance and are more likely to produce a urolith with an irregular surface. Calcium oxalate crystals precipitate more readily in urine with an acidic pH.31

Hypercalcemia is a predisposing factor for calcium oxalate urolith formation and has been reported in 35% of cats with uroliths and in about 4% of dogs with uroliths.14,30,31 The hypercalcemia observed in this cat population is usually idiopathic, while dogs most often have primary hyperparathyroidism. In dogs, hyperadrenocorticism, which has been associated with hypercalciuria, also increases the risk of developing calcium oxalate uroliths.32 Hypercalciuria contributes to calcium oxalate formation in some dogs and cats as a result of hyperabsorption of calcium from the intestines or renal leak hypercalciuria, which is associated with decreased renal tubular calcium reabsorption.33 When possible, treat these underlying conditions through diet, medication, or surgery to lessen the risk of calcium oxalate urolithiasis.

Treatment. Treating calcium oxalate uroliths is limited to surgical removal, voiding urohydropropulsion, and lithotripsy since no method of medical dissolution is available. Leaving the uroliths in place may be a reasonable option in some asymptomatic patients. Continue monitoring the patient for the development of clinical signs and employing measures to prevent further calcium oxalate formation.

Prevention. In dogs, recurrence rates of up to 50% within three years of initial diagnosis have been reported,24 so preventing initial urolithiasis is key. Although many conflicting factors have been reported regarding the best diet for calcium oxalate urolith prevention, protein and oxalate restriction and urine alkalinization are recommended.31 Diets formulated for oxalate urolith prevention in dogs and cats are listed in Table 1.

In addition, in dogs Prescription Diet Canine w/d and potassium citrate (e.g. Urocit-K—Mission Pharmacal, 75 mg/kg orally twice a day) are also options, especially in obese patients or those prone to developing pancreatitis.24 And in some hypercalcemic cats with calcium oxalate uroliths, Prescription Diet Feline w/d (Hill's Pet Nutrition) and potassium citrate (75 mg/kg orally twice a day) normalizes calcium concentrations.34,35

In people, potassium citrate's alkalinizing effect helps decrease bone calcium release and promote calcium excretion in a more soluble form, calcium citrate.24,25 These same beneficial effects may occur with potassium citrate administration in dogs and cats. The desired urine pH range for preventing calcium oxalate urolith formation is 6.5 to 7.5.

If diet or diet plus potassium citrate fails to prevent calcium oxalate urolith recurrence, consider adding thiazide diuretics (hydrochlorothiazide 2 to 4 mg/kg orally twice a day)33 to decrease the calcium excretion in the urine.36,37 Although unproven in cats, thiazide diuretics decrease urinary calcium excretion in people and dogs with calcium oxalate urolithiasis. A study in dogs indicated that feeding them Prescription Diet u/d (Hill's Pet Nutrition) in conjunction with hydrochlorothiazide administration enhanced reduction of urine calcium.36 Thiazide diuretics are contraindicated in hypercalcemic patients because they may aggravate the hypercalcemia.

Use loop diuretics, such as furosemide, with caution in patients at risk for calcium oxalate urolithiasis since their mechanism of action may increase the formation of such uroliths by augmenting calcium urine excretion. Avoid supplementation of vitamin C, an oxalate precursor, and vitamin D, an aid to the gastrointestinal absorption of calcium, in patients with calcium oxalate urolithiasis.31

Urate (purine)

The third most common noncompound type of urolith reported in dogs and cats is purine. Most purine uroliths are composed of urates (uric acid and uric acid salts).24,34 Unlike struvite and calcium oxalate uroliths, urate uroliths have varied relatively little in incidence over the last 20 years, accounting for about 4.6% of uroliths in cats and 8% in dogs.14,22

Characteristics. Ammonium urate crystals are large and irregular in shape, and uric acid crystals are slender and hexagonal. These crystals form small; smooth; round; light-yellow, light-brown, or light-green radiolucent uroliths that are found most frequently in the bladder or urethra. Positive or double-contrast cystography or urethrography or high-frequency ultrasonography is usually needed for detection.24,39

Dalmatians and English bulldogs are the classic breeds associated with this urolith because of inherent differences in the way that uric acid is metabolized and transported in these dogs. Male Dalmatians and English bulldogs are affected more commonly than females. Dalmatians are thought to have impaired transport of uric acid into the liver and to have increased excretion of uric acid into the urine. All Dalmatians appear to have these alterations in uric acid metabolism, but only a small percentage actually develop urate uroliths. The Dalmatians developing these uroliths are most commonly affected at 1 to 4 years of age, with a decrease in incidence after 6 years of age.14,24 Although the cause of the English bulldog's predisposition to urate urolith formation is not clearly defined, it has been theorized that a renal proximal tubular defect and alterations in purine liver metabolism cause increased urate urolith formation in this breed.38

Dogs other than Dalmatians and bulldogs and some cats can be at risk for developing urate uroliths because of changes in metabolism related to hepatic disease, especially portovascular anomalies, including hepatic microvascular dysplasia.39 Miniature schnauzers, Yorkshire terriers, and Shih Tzus are at increased risk.24 Urate uroliths can be found in both male and female dogs with portovascular anomalies and are commonly diagnosed when the patient is < 3 years old.39

In many cats, urate urolith formation is idiopathic but may occur as a result of portovascular anomalies.25,34 No known sex or breed predisposition has been established for cats.34 Although urate uroliths occur most commonly in cats that are < 4 years old, urate uroliths associated with portovascular anomalies are frequently found in cats < 1 year of age.34

Treatment. In dogs, urate uroliths can be medically dissolved either completely or partially in about two-thirds of the cases in which an appropriate calculolytic diet is given.14,24 The calculolytic diet of choice for dogs is Prescription Diet u/d, which is low in dietary purines, alkalinizes urine, and forms a more dilute urine. Because of nutrient restrictions, Prescription Diet u/d should not be given to pregnant or lactating bitches or immature dogs and should be given with caution to English bulldogs, which may develop dilated cardiomyopathy because of carnitine deficiency.14,24 The time required for urolith dissolution averages about three or four months. It may be necessary to add allopurinol (15 mg/kg orally twice a day), a competitive inhibitor of the enzyme xanthine oxidase, to the dissolution protocol.39 In cats, allopurinol (7.5 mg/kg orally twice a day) and Prescription Diet Feline k/d (Hill's Pet Nutrition) can be used in a dissolution protocol.30 Administering allopurinol to treat or prevent urate uroliths may result in xanthine urolith formation because allopurinol inhibits xanthine oxidase. Therefore, always feed a purine-restricted diet (e.g. Prescription Diet Canine u/d, Prescription Diet Feline k/d) to patients receiving allopurinol.

Urate uroliths in cats and urate uroliths associated with portosystemic shunts often cannot be medically dissolved.13 Consequently, voiding urohydropropulsion, lithotripsy, or surgical intervention is often required to remove urate uroliths in these patients. Spontaneous dissolution of urate uroliths after correcting portovascular anomalies may occur but has not been documented with published studies.24 Urinary tract infections occur commonly with urate uroliths; treat these with appropriate antibiotics.

Prevention. Preventing urate uroliths in dogs can often be accomplished by feeding Prescription Diet Canine u/d with or without allopurinol (5 to 10 mg/kg orally once or twice a day). Preventing urate uroliths in cats is generally successful by feeding them a kidney disease management diet such as Prescription Diet Feline k/d, which is alkalinizing and protein-restricted.34 Patients with urate uroliths associated with portovascular shunts should undergo surgical correction for the anomaly, if possible, to prevent further urolith formation.

Xanthine (purine)

Xanthine is a purine urolith recognized more recently in cats but also reported in Cavalier King Charles spaniels and dachshunds. These two dog breeds are thought to have an inborn error of purine metabolism, which leads to xanthine formation.24,40 In cats, a familial or congenital defect in the activity of xanthine oxidase is suspected to be the primary cause of xanthine urolith formation.41

Characteristics. Xanthine crystals resemble uric acid crystals or are amorphous. Xanthine uroliths are usually a few millimeters in diameter, have a smooth surface, and are yellow, tan, or light-brown. The uroliths are radiolucent and often must be detected through positive double-contrast cystography or urethrography or high-frequency ultrasonography. Xanthine uroliths have been found primarily in the lower urinary tract, although they occasionally occur in the upper urinary tract. Affected cats' urine may be a mustard-yellow color. Male cats appear to be predisposed to xanthine formation, and the average age of affected cats at the time of diagnosis is 2.8 years.34 An incidence of 0.1% in cats was reported by the Minnesota Urolith Center in 2006.22 Although allopurinol administration predisposes both cats and dogs to xanthine formation, most affected cats have not received this drug.34

Treatment and prevention. No medical dissolution protocol exists for this urolith type. Treatment consists of removal or lithotripsy. The recommended prevention protocol for dogs and cats consists of feeding them a protein-restricted, alkalinizing diet such as Prescription Diet k/d.41 Because allopurinol administration without purine restriction can cause xanthine urolith formation, always feed a purine-restricted diet to patients receiving allopurinol for any reason.23,39,42

Cystine

Cystine uroliths are uncommon in dogs (1% prevalence)21 and even less common in cats (< 1% prevalence).34

Characteristics. Cystine crystals are large, flat, and hexagonal, and their presence in urine should always be considered abnormal. Cystine crystals precipitate in acid urine to form uroliths that are small, spherical, and light-yellow, light-brown, or light-green. These uroliths are relatively radiolucent and commonly require contrast cystography or urethrography or ultrasonography for detection.

In dogs and cats, cystine urolith formation is associated with an inherited disorder that causes insufficient renal tubular reabsorption of cystine and other amino acids.43 Affected dogs are commonly 4 to 6 years old at the time that cystine uroliths are detected. Affected dog breeds include English bulldogs, Newfoundlands, dachshunds, Irish terriers, basset hounds, and bullmastiffs.14 Male dogs are more commonly affected than female dogs except in Newfoundlands, in which both sexes seem equally affected.

Male and female cats appear to be equally affected, and cystine urolithiasis is diagnosed at a mean age of 4.1 years. Domestic shorthaired and Siamese cats are the most commonly affected.25,44

Treatment. An alkalinizing, low-protein diet, such as Prescription Diet u/d, is recommended for treating cystine uroliths in dogs. Thiol disulfide exchange drugs, d-penicillamine and MPG, or tiopronin (Thiola—Mission Pharmacal), are used to dissolve these uroliths in dogs. These drugs combine with the precursors of cystine to produce a more soluble product. In dogs, combining a thiol exchange drug with Prescription Diet u/d appears to enhance cystine urolith dissolution.45 D-penicillamine is administered at a dosage of 15 mg/kg orally twice a day, and tiopronin is administered at a dosage of 20 mg/kg orally twice a day.24 The thiol disulfide exchange drugs are most effective at a neutral to alkaline urine pH.

D-penicillamine's main side effect is vomiting, which can usually be avoided by giving the drug with food, administering an antiemetic, or decreasing the dose slightly. Side effects do not occur as commonly with tiopronin administration but can include behavioral changes, myopathy, proteinuria, thrombocytopenia, immune-mediated anemia, skin lesions, lethargy, elevated liver enzyme activities, or a sulfur odor to the urine.24

Dissolution will be successful in about two-thirds of the dogs treated and requires about one to three months. Monitoring dissolution progress by imaging may require ultrasonography or double-contrast cystography.

No proven cystine urolith dissolution protocol is available for cats. Consider surgical removal, lithotripsy, or voiding urohydropropulsion for eliminating cystine uroliths in cats or in dogs in which medical dissolution is not acceptable or successful.

Prevention. The high recurrence rate of cystine uroliths and the inherited predisposing defect make prevention important in dogs that have experienced an episode of cystine urolith formation. A prevention protocol consists of administering tiopronin (15 mg/kg orally twice a day), adding water to the patient's food, and alkalinizing the urine with potassium citrate (100 to 150 mg/kg once a day or in two divided doses/day).14 The goal of alkalinization should be to achieve a urine pH of 7 to 7.5.24 An alternative prevention protocol calls for feeding Prescription Diet u/d plus administering either tiopronin or d-penicillamine at 10 to 15 mg/kg orally every 12 hours.46 Although Prescription Diet u/d is considered a maintenance diet, it has a low protein content, so monitor dogs fed this diet long-term for protein depletion by performing a serum chemistry profile at least every six months.

Although the incidence of feline cystine uroliths is low, the frequency of recurrence in affected cats appears high.44 For cats, a diet for managing kidney disease, such as canned or moistened dry Prescription Diet k/d or similar alkalinizing renal failure diets from other manufacturers, is recommended.

Silicate

Silicate uroliths are uncommon in dogs, accounting for < 1% of all urolith types analyzed with the Minnesota Urolith Center from 1981 to 2006.21 Silicate uroliths are rarely reported in cats.5,40

Characteristics. These uroliths are grayish-white to brown and frequently look like jackstones.47 They are radiopaque and found most frequently in the bladder and urethra. Silicate uroliths are composed primarily of amorphous silica crystals. A predisposition exists for German shepherds and Old English sheepdogs.24

The cause of silicate uroliths is unknown but may be diet-related. Diets high in corn gluten or rice and soybean hulls are suspected to increase the incidence of silicate urolith formation.24 No relationship has been established between urine pH and silicate urolith formation.

Treatment and prevention. No method of medical dissolution is available, and surgical removal is often necessary, although voiding urohydropropulsion can be attempted if the uroliths are small enough. Lithotripsy is another treatment option. Recurrence is possible but uncommon. The only recommendations for prevention are to increase water consumption and avoid diets high in plant proteins. Prescription Diet d/d (Hill's Pet Nutrition) may be appropriate for prevention because of its low plant protein content.

Compound

Compound uroliths are found in cats (< 5% prevalence)22 and dogs (8.5% prevalence).21

Characteristics. Compound uroliths are uroliths in which the center is at least 70% one mineral type and the outer layer is at least 70% of another mineral type.21

Treatment and prevention. Since the two primary mineral types may have conflicting treatment protocols, quantitative analysis to determine composition is especially important.48 In general, treat and prevent these uroliths by using the appropriate protocol for each primary mineral type as identified above. Compound uroliths containing calcium oxalate have become more prevalent during the last several years,14 limiting medical dissolution opportunities. When a compound urolith has calcium oxalate as one of the primary mineral types and the second mineral type is one that is amenable to medical dissolution, it is advisable to direct prevention efforts toward the calcium oxalate component. When struvite is combined with calcium oxalate in a compound urolith, eradicate any urinary tract infection as well.48

Dried solidified blood

The dried solidified blood urolith is a composition recently recognized in cats.49

Characteristics. These uroliths are found in both the upper and lower urinary tract and differ from other uroliths in that they usually contain no crystalline material. Dried solidified blood uroliths appear to be formed from organic material, are generally radiolucent, and are not identifiable by ultrasonography.49 Contrast radiography may suggest urinary tract obstruction but not reveal a discrete urolith. No known sex predisposition exists. Domestic shorthaired and longhaired cats are most commonly affected. The mean age of cats with dried solidified blood uroliths in a report of 49 affected cats was 9 years.49

Treatment and prevention. No medical dissolution or prevention protocols are available. Because of the difficulty in identifying the urolith by imaging, surgical removal has been the primary treatment method. Because hematuria was identified in all cats for which urinalysis results were available, searching for inflammatory or ischemic causes of hematuria is recommended. In addition, increasing fluid intake (e.g. feeding canned food) is encouraged.

Nephroliths and ureteroliths

Although most uroliths in dogs and cats are found in the bladder or urethra, uroliths are also occasionally located in the renal pelves or ureters.

Characteristics. Upper urinary tract uroliths are most commonly composed of struvite or calcium oxalate, with calcium oxalate being the more prevalent.50

Treatment. In cases in which nephroliths or ureteroliths are suspected to be primarily struvite, medical dissolution can be attempted, provided that an emergency circumstance does not preclude that option. Medical dissolution of a suspected struvite ureterolith is unlikely since the urolith's location does not allow consistent contact with urine that is acidic and undersaturated with struvite-forming minerals as a result of dietary therapy.10 Surgical intervention or lithotripsy is the primary option when an upper urinary tract urolith is suspected to be composed of calcium oxalate and warrants removal.

Ureteroliths will sometimes pass into the bladder or move retrograde into the kidney pelvis.50 In some cases, ureterolith passage into the bladder can be facilitated by administering smooth muscle relaxants such as prazosin (Minipress—Pfizer; 0.25 to 0.5 mg/cat orally twice a day; 1 mg/15 kg orally once or twice a day in dogs), fluid therapy, and diuretics. Amitriptyline can also be used in dogs for ureteral smooth muscle relaxation (1 to 2 mg/kg orally once a day). If the ureterolith has not passed from the ureter in three to five days with medical management, surgical intervention or lithotripsy may need to be considered.

Consider removing an affected kidney and ureter if their function is severely impaired because of a nephrolith and the other kidney is functioning adequately as demonstrated by the results of laboratory tests and an excretory urogram or nuclear scintigraphy. Removing a urolith by surgically incising the renal pelvis or ureter is also an option but may cause permanent damage to these organs. The introduction of a percutaneous approach to surgical incision of the kidney for the purpose of urolith extraction, lithotripsy, or ureteral stent placement holds promise for decreasing associated damage to the affected area.16,17

In general, nephrotomy and ureterotomy should only be undertaken if the urolith is severely compromising renal function; is associated with severe pain, hematuria, or infection; or is steadily enlarging and causing obvious damage to kidney tissue. Otherwise, the best option is often monitoring the patient's status by periodically evaluating the results of serum chemistry profiles, urinalyses, and abdominal imaging; observing for progressive clinical signs; providing pain management as needed; and implementing a preventive plan appropriate for the suspected urolith type. The evaluation interval will vary with the patient's condition. Relatively asymptomatic patients may only require evaluation every two to three months, while patients exhibiting more clinical signs may warrant daily to weekly evaluation.

Mary Bowles, DVM, DACVIM

Department of Veterinary Clinical Sciences

Center for Veterinary Health Sciences

Oklahoma State University

Stillwater, OK 74078

REFERENCES

1. Osborne CA, Lulich JP, Ulrich LK, et al. Feline crystalluria. Detection and interpretation. Vet Clin North Am Small Anim Pract 1996;26(2):369-391.

2. Feeney DA, Weichselbaum RC, Jessen CR, et al. Imaging canine urocystoliths. Detection and prediction of mineral content. Vet Clin North Am Small Anim Pract 1999;29(1):59-72.

3. Weichselbaum RC, Feeney DA, Jessen CR, et al. Urocystolith detection: comparison of survey, contrast radiographic and ultrasonographic techniques in an in vitro bladder phantom. Vet Radiol Ultrasound 1999;40(4):386-400.

4. Lulich JP, Osborne CA, Sanderson SL, et al. Voiding urohydropropulsion. Lessons from 5 years of experience. Vet Clin North Am Small Anim Pract 1999;29(1):283-291.

5. Lulich JP, Osborne CA, Carlson M, et al. Nonsurgical removal of urocystoliths in dogs and cats by voiding urohydropropulsion. J Am Vet Med Assoc 1993;203(5):660-663.

6. Lulich J, Osborne CA. Beyond the stone age: minimally invasive techniques, in Proceedings. 25th Am Coll Vet Intern Med Forum, 2007.

7. Lulich JP, Osborne CA, Polzin DJ, et al. Incomplete removal of canine and feline urocystoliths by cystotomy (abstr). J Vet Intern Med 1993;7:124A.

8. Grant DC, Werre SR, Gevedon ML. Holmium: YAG laser lithotripsy for urolithiasis in dogs. J Vet Intern Med 2008;22(3):534-539.

9. Adams LG, Berent AC, Moore GE, et al. Use of laser lithotripsy for fragmentation of uroliths in dogs: 73 cases (2005-2006). J Am Vet Med Assoc 2008;232(11):1680-1687.

10. Osborne CA, Lulich JP, Polzin DJ, et al. Medical dissolution and prevention of canine struvite urolithiasis. Twenty years of experience. Vet Clin North Am Small Anim Pract 1999;29(1):73-111.

11. Forrester SD. Management of feline lower urinary tract disease, in Proceedings. Hill's Global Symp Feline Care 2006;51-60.

12. Lekcharoensuk C, Osborne CA, Lulich JP, et al. Association between dietary factors and calcium oxalate and magnesium ammonium phosphate urolithiasis in cats. J Am Vet Med Assoc 2001; 219(9):1228 -1237.

13. Chew DJ, Buffington CA. Feline urolithiasis, in Proceedings. VCA Antech Semin: Update on Nephro/Urol 2006;1-5.

14. Chew DJ, Buffington CA. Diets and drugs for canine urolithiasis, in Proceedings. VCA Antech Semin: Update on Nephrol/Urol 2006.

15. Lulich JP, Osborne CA, Thumchai R, et al. Management of canine calcium oxalate urolith recurrence. Compend Contin Educ Pract Vet 1998;20(2):178-189.

16. Berent A. Interventional endoscopy of the urinary system in Proceedings. 25th Am Coll Vet Intern Med Forum 2007.

17. Berent A. Interventional radiology and endourology of the urinary system, in Proceedings. Am Coll Vet Surg 2006.

18. Bovee KC, McGuire T. Qualitative and quantitative analysis of uroliths in dogs: definitive determination of chemical type. J Am Vet Med Assoc 1984;185(9):983-987.

19. Osborne CA, Lulich JP, Kruger JM, et al. Medical dissolution of feline struvite urocystoliths. J Am Vet Med Assoc 1990;196(7):1053-1063.

20. Houston DM, Rinkardt NE, Hilton J. Evaluation of the efficacy of a commercial diet in the dissolution of feline struvite bladder uroliths. Vet Ther 2004;5(3):187-201.

21. Osborne CA, Lulich JP. Perspectives: analysis of 275,000 uroliths. DVM Newsmagazine July 1, 2006. Available at: http://veterinarynews.dvm360.com/dvm/article/articleDetail.jsp?id=360567&sk=&date=&pageID=1.

22. Osborne CA, Lulich JP. Changing trends in composition of feline uroliths and urethral plugs. DVM Newsmagazine April 1, 2006. Available at http://veterinarynews.dvm360.com/dvm/article/articleDetail.jsp?id=408450&sk=&date=&pageID=2.

23. Cannon AB, Westropp JL, Ruby AL, et al. Evaluation of trends in urolith composition in cats: 5,230 cases (1985-2004). J Am Vet Med Assoc 2007;231(4):570-576.

24. Adams LG, Syme HM. Canine lower urinary tract diseases. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 6th ed. St. Louis, Mo: Elsevier Saunders, 2005;1850-1874.

25. Westropp JL, Buffington CAT, Chew DJ, et al. Feline lower urinary tract diseases. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 6th ed. St. Louis, Mo: Elsevier Saunders, 2005;1828-1850.

26. Bartges JW. Emerging from the stone age: an update on urolithiasis. VIN Rounds: March 25, 2007. Available at: http://www.vin.com/Members/SearchDB/rounds/lc070325.htm

27. Osborne CA, Unger LK, Lulich JP. Canine and feline nephroliths. In: Bonagura JD, Kirk RW, eds. Kirk's current veterinary therapy XII: small animal practice. Philadelphia, Pa: WB Saunders Co, 1995;981-985.

28. Ling GV. Urinary stone disease. In: Lower urinary tract diseases of dogs and cats. Philadelphia, Pa: Mosby Year Book, 1995;144-177.

29. Lulich JP, Osborne CA, Thumchai R, et al. Epidemiology of canine calcium oxalate uroliths. Identifying risk factors. Vet Clin North Am Small Anim Pract 1999;29(1):113-122.

30. Hostutler RA, Chew DJ, DiBartola SP. Recent concepts in feline lower urinary tract disease. Vet Clin North Am Small Anim Pract 2005;35(1):147-170.

31. Osborne CA, Lulich JP, Thumchai R, et al. Feline urolithiasis. Etiology and pathophysiology. Vet Clin North Am Small Anim Pract 1996;26(2):217-232.

32. Hess RS, Kass PH, Ward CR. Association between hyperadrenocorticism and development of calcium-containing uroliths in dogs with urolithiasis. J Am Vet Med Assoc 1998;212(12):1889-1891.

33. Bartges JW, Kirk C, Lane IF. Update: management of calcium oxalate uroliths in dogs and cats. Vet Clin North Am Small Anim Pract 2004;34(4):969-987.

34. Bartges JW, Kirk CA. Nutrition and lower urinary tract disease in cats. Vet Clin North Am Small Anim Pract 2006;36(6):1361-1376.

35. McClain HM, Barsanti JA, Bartges JW. Hypercalcemia and calcium oxalate urolithiasis in cats: a report of five cases. J Am Anim Hosp Assoc 1999;35(4):297-301.

36. Lulich JP, Osborne CA, Lekcharoensuk C, et al. Effects of hydrochlorothiazide and diet in dogs with calcium oxalate urolithiasis J Am Vet Med Assoc 2001;218(10):1583-1586.

37. Pearle MS, Roehrborn CG, Pak CY. Meta-analysis of randomized trials for medical prevention of calcium oxalate nephrolithiasis. J Endourol 1999;13(9):679-685.

38. Bartges JW, Sanderson S, Osborne CA, et al. Urolithiasis in English bulldogs, in Proceedings. 16th Am Coll Vet Intern Med Forum 1998.

39. Bartges JW, Osborne CA, Lulich JP, et al. Canine urate urolithiasis: etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 1999;29(1):161-191.

40. Houston DM, Moore AE, Favrin MG, et al. Canine urolithiasis: a look at over 16,000 urolith submissions to the Canadian Veterinary Urolith Centre from February 1998 to April 2003. Can Vet J 2004;45(3):225-230.

41. Osborne CA, Lulich JP, Lekcharoensuk C, et al. Feline xanthine urolithiasis: a newly recognized cause of feline lower urinary tract disease, in Proceedings. 21st Am Coll Vet Intern Med Forum 2003.

42. Ling GV, Ruby AL, Harrold DR, et al. Xanthine-containing urinary calculi in dogs given allopurinol. J Am Vet Med Assoc 1991;198(11):1935-1940.

43. Case LC, Ling GV, Franti CE, et al. Cystine-containing urinary calculi in dogs: 102 cases (1981-1989). J Am Vet Med Assoc 1992;201(1):129-133.

44. Osborne CA. How would you manage urocystoliths in a female Siamese cat? DVM Newsmagazine February 1, 2003. Available at: http://veterinarynews.dvm360.com/dvm/article/articleDetail.jsp?id=46550.

45. Osborne CA, Sanderson SL, Lulich JP, et al. Canine cystine urolithiasis. Cause, detection, treatment, and prevention. Vet Clin North Am Small Anim Pract 1999;29(1):193-211.

46. Nelson RW, Couto CG. Canine urolithiasis. Small animal internal medicine. 2nd ed. St. Louis, Mo: Mosby, 1998;638-645.

47. Aldrich J, Ling GV, Ruby AL, et al. Silica-containing urinary calculi in dogs (1981-1993). J Vet Intern Med 1997;11(5):288-295.

48. Lulich JP, Osborne CA. Compound uroliths: treatment and prevention. In: Bonagura JD, ed. Kirk's current veterinary therapy XIII: small animal practice. Philadelphia, Pa: WB Saunders Co, 2000;874-877.

49. Westropp JL, Ruby AL, Bailiff NL, et al. Dried solidified blood calculi in the urinary tract of cats. J Vet Intern Med 2006;20(4):828-834.

50. Dalby AM, Adams LG, Salisbury SK, et al. Spontaneous retrograde movement of ureteroliths in two dogs and five cats. J Am Vet Med Assoc 2006;229(7):1118-1121.