Canine uroliths (Proceedings)

Diagnosis of urolithiasis may be aided by historical information such as the previous occurrence of uroliths or owner observation of symptoms compatible with the presence of uroliths. Predisposition to urolithiasis may be indicated by case signalment or pre-existing medical conditions favoring urolith formation. Laboratory data base information (CBC, biochemistry profile, urinalysis) does not indicate specifically the presence of a urolith but provides valuable information in regard to predisposing or complicating medical conditions. In addition, urinalysis findings such as pH, evidence of bacterial infection, and the presence of specific crystal types can also aid in determining the most likely composition of uroliths detected. Urinalysis is best performed within 30 minutes of sample collection. Refrigeration will help preserve the urine sample but can alter both the chemical and sediment findings. In particular, crystal formation can be enhanced by temperature and pH changes which may occur with time and refrigeration, causing misinterpretation of the urinalysis results. Physical examination of the patient may give an indication of the presence of uroliths if a firm object is palpated in the bladder or if very small uroliths are observed in voided urine or mucoid discharge from the penis or vulva. Rectal examination may reveal pelvic urethroliths. In most cases definitive diagnosis requires imaging procedures such as survey abdominal and/or urethral radiography, ultrasonography or contrast radiography. The entire length of the urinary tract should be surveyed to make certain that uroliths are not present in muliple locations and to identify any factors predisposing the patient to urolith formation. Ultrasonography is a good initial imaging tool to detect uroliths; however, ultrasonography does not provide information concerning the radiodensity of uroliths or the shape of uroliths. In addition, unless the size of the patient allows the use of a rectal transducer, the pelvic urethra cannot be imaged with ultrasonography. Survey radiographs can detect radiodensity of uroliths and give some information about the size and contour of uroliths. Survey radiographs are also generally the most cost effective and available noninvasive procedure for initial evaluation of uroliths. Although high-frequency ultrasonoraphy compared favorably to double contrast cystography in the detection of urocystoliths and the determination of urolith numbers in one study, double contrast cystography has the additional benefit of being a sensitive and specific indicator of urolith shape and size. Determining exact numbers of uroliths with any of the imaging modalities can be challenging in some cases.

Following the diagnosis of urolithiasis, therapy and prevention depend upon factors such as urolith composition, associated etiology, and location of the urolith in the urinary tract.

Struvite

The struvite (magnesium ammonium phosphate hexahydrate) urolith is one of the most common uroliths occurring in the dog. Although canine uroliths composed of struvite have been the most prevalent category of stone composition for a total time period spanning 25 years (1981 – 2005, 43.5%) according to one study20, a steady decline in occurrence of canine struvite uroliths during that same time period has resulted in struvite becoming the second most prevalent urolith composition in the dog beginning in 2004 (39%). The shift in urolith prevalence in the dog has been theorized to be the result of commercial maintenance diet reformulation as well as the increased use of therapeutic diets designed to dissolve or prevent uroliths.

Struvite uroliths are frequently spherical or pyramidal, radiodense, and vary greatly in size. Struvite crystals precipitate out more readily in alkaline urine and have an angular, prism-like appearance.

Unlike the cat, the majority of canine struvite uroliths have an infectious etiology although sterile sruvite uroliths can occur. Canine Infection-related uroliths occur more commonly in female patients between 2 and 9 years-of-age. Struvite urolith formation has a breed predisposition for the miniature schnauzer, shih tzu, bichon frise, miniature poodle, cocker spaniel, and lhasa apso.

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

Feeding a calculolytic diet such as Hill's canine s/d® can dissolve both sterile and infection-related struvite urocystoliths and nephroliths, by creating an acidic, dilute urine undersaturated with magnesium, ammonium, and phosphorus. The time for urolith dissolution is variable, but averages about 2 - 3 months for infection-related uroliths and 3 – 6 weeks for sterile uroliths.23,24,25 Dissolution will occur more rapidly with infection-related struvite uroliths when an appropriate antibiotic is administered concurrently. Antibiotic therapy is best determined by culture and sensitivity testing of urine obtained by cystocentesis. Ideally, urine culture should be performed prior to the initiation of antibiotic administration and periodically during the dissolution process. By evaluating serial urinalyses and abdominal radiographs or ultrasound at approximately 4-week intervals, dissolution therapy can be altered as needed for individual patients. Urinalysis findings compatible with ongoing infection (bacteriuria, pyuria, alkaluria) indicate the need to reassess antibiotic therapy through urine culture and sensitivity testing. Diagnostic imaging is the primary means of determining the success of the dissolution therapy. The calculolytic diet and antibiotic administration should be continued for one month following complete dissolution of uroliths as established by imaging. Hill's s/d® is not a maintenance diet and should not be fed for longer than 6 months. The nutrient restrictions, fat content, and increased sodium content of Hill's s/d® make it unsuitable as a diet for puppies, pregnant or lactating pets, and pets with heart failure, hypertension, or renal failure. In a recent study with as yet unpublished results, an alternative protocol for treating infection-related struvite uroliths in dogs has resulted in preliminary evidence that dissolution of these uroliths may be achieved by feeding a maintenance, non-calculolytic diet(e.g, Science Diet Adult Original {Hill's Pet Nutrition}, Dog Chow {Purina}) when combined with antibiotic therapy and the urinary acidifier d,l methionine (Methioform® - 100 mg/kg PO q12 hrs) 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. Calcium phosphate and calcium carbonate phosphate are minerals which are occasionally associated with struvite uroliths and may interfere with medical dissolution therapy.

Prevention of sterile struvite uroliths can be accomplished by feeding any of many available diets that increase urine volume, decrease urine pH to < 6.8, and decrease excretion of magnesium, ammonium and phosphorus (e.g., Royal Canin canine Control Formula®). Hill's canine w/d® can be used in struvite prevention programs when patient obesity is a concern. Preventative diets for struvite uroliths are less restrictive than the calculolytic diets, but are still not satisfactory for puppies, lactating patients, or pregnant patients. Although such a diet can be fed for prevention to patients with infection-related struvite uroliths, special dietary management is not specifically indicated because the key to prevention is eradication of bacterial infection and subsequent monitoring for recurrence of infection by periodically checking urinalyses and urine cultures.

Calcium Oxalate

Uroliths of calcium oxalate composition have had a reciprocal relationship with uroliths composed of struvite over the last several years in the dog. As the incidence of struvite has gradually decreased in the dog, the incidence of canine calcium oxalate uroliths has steadily increased, surpassing struvite in prevalence (41% in 2005, Minnesota Urolith Center). Canine calcium oxalate urolith formation has been reported to have a male gender predisposition. Small breed dogs are predisposed and include the miniature schnauzer, lhasa apso, Yorkshire terrier, bichon frise, shih tzu, and miniature poodle. Dogs ages 8 – 12 years have been found to have the greatest risk for developing calcium oxalate uroliths.

Calcium oxalate uroliths are very radiodense and variable in size. Calcium oxalate uroliths are made up of two different types of crystals, monohydrate (dumbbell or "picket fence" shape) and dihydrate ("maltese cross" appearance), resulting in uroliths which range from smooth to jagged in contour. Calcium oxalate crystals precipitate out more readily in urine with an acidic pH.

Hypercalcemia can be a predisposing factor for calcium oxalate urolith formation and has been reported to occur in approximately 4% of dogs with this type of urolith. Dogs with associated hypercalcemia most often have primary hyperparathyroidism. Hyperadrenocorticism also increases the risk for development of calcium oxalate uroliths. Hypercalciuria contributing to calcium oxalate formation may also occur in some dogs as a result of hyperabsorption of calcium from the intestine or renal leak hypercalciuria which is associated with decreased renal tubular reabsorption of calcium. When possible, treating these underlying problems through diet, medication, or surgery can diminish the risk for development of calcium oxalate uroliths.

No method of medical dissolution of this type of urolith is available. Elimination of calcium oxalate uroliths requires surgical removal, voiding urohydropropulsion, or lithotripsy. Leaving the uroliths in place may be a reasonable option in some asymptomatic patients, monitoring the patient for the development of clinical signs and employing measures to prevent further calcium oxalate formation. Regardless of the approach used in treatment, taking preventative steps is particularly important due to reported recurrence rates as high as 50% in the dog. The most consistent recommendations for prevention include urine alkalinization (desired pH range 6.5 – 7.5) and dietary protein and oxalate restriction. Diets formulated for oxalate prevention (as well as other urinary problems) in dogs include Hill's u/d® and Royal Canin's Urinary s/o®. In addition, Hill's canine w/d® plus potassium citrate (Urocit K® - 75 mg/kg PO q12 hrs) can also be used, especially for obese patients or those prone to developing pancreatitis. The addition of thiazide diuretics (hydrochlorothiazide, 2 – 4 mg/kg PO every 12 hours) to the prevention regimen may be considered in non-hypercalcemic patients in an attempt to decrease the excretion of calcium in the urine. Other considerations in prevention include avoiding the administration of loop diuretics such as furosemide,medicinal rhubarb, and vitamins C and D due to the possibility that these agents could enhance calcium oxalate formation.

Purine (Urate, Xanthine)

The third most common type of non-compound urolith reported in the dog is of purine origin, specifically urate. The incidence of urate uroliths in the dog has been reported as 8%. The Dalmatian and the English bulldog are the classic dog breeds associated with this urolith as a result of inherent differences in the way that uric acid is metabolized and transported in these breeds. Male Dalmatians and English bulldogs are affected more commonly than females. The Dalmatian is 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. Those Dalmatians developing uroliths are most commonly affected at 1 – 4 years-of-age with a decrease in incidence after 6 years of age. It is theorized that the English bulldog is predisposed to urate urolith formation due to a renal proximal tubular defect and alterations in purine liver metabolism. Some dog breeds are at risk for developing urate uroliths as a result of metabolism changes related to hepatic disease, especially portovascular anomalies. Dog breeds in this category include the miniature schnauzer, Yorkshire terrier, and shih tzu. Unlike urate formation in the Dalmation and English bulldog a clear gender predisposition has not been found in dogs with urate uroliths associated with portovascular anomalies. Urate uroliths resulting from portovascular disorders are most frequently identified in dogs < 3 years-of-age. Urate uroliths are formed from ammonium urate crystals, which are large and irregular in shape, and uric acid crystals, which are slender and hexagonal. These crystals form small, smooth, and generally round radiolucent uroliths that can be light yellow, brown, or green. Urate uroliths are found most frequently in the bladder or urethra and usually require positive or double-contrast radiographic studies or high frequency ultrasonography for detection.

Canine urate uroliths can be medically dissolved either completely or partially in approximately 2/3 of the cases in which an appropriate calculolytic diet is used. The calculolytic diet of choice for dogs is Hill's u/d®, which is low in dietary purines, alkalinizing, and forms a more dilute urine. Because of its restrictive nature u/d® should not be used in pregnant or lactating bitches, immature dogs, or English bulldogs, which may develop dilated cardiomyopathy as a consequence of carnitine deficiency. The time required for urolith dissolution averages about 3 – 4 months. It may be necessary to add allopurinol (15 mg/kg PO q12 hrs), a competitive inhibitor of the enzyme xanthine oxidase, to the dissolution protocol. Urate uroliths associated with portosystemic shunts often cannot be medically dissolved. Consequently, voiding urohydropropulsion, surgical removal, or lithotripsy is often required to remove urate uroliths in patients with portovascular anomalies. Urinary tract infection occurs commonly with urate uroliths and should be treated with appropriate antibiotics.

Prevention of urate uroliths in the dog can often be accomplished by feeding Hill's u/d® with or without the addition of allopurinol (5 – 10 mg/kg PO q12 - 24 hrs). A low purine diet should always be fed with allopurinol to prevent xanthine urolith formation. Patients with urate uroliths associated with portovascular shunts should undergo surgical correction for the anomaly, if possible, to prevent further urolith formation.

Xanthine is a type of purine urolith reported in the Cavalier King Charles spaniel (CKCS) and dachshund. In the CKCS and dachshund xanthine formation is believed to result from an inborn error of purine metabolism. Xanthine uroliths are usually a few mm in diameter, have a smooth surface, and are usually yellow, tan, or light brown in color. Xanthine crystals resemble uric acid crystals or are amorphous. Xanthine uroliths are radiolucent and often must be detected through double contrast radiographic studies or ultrasonography. Xanthine uroliths have been found primarily in the lower urinary tract although a few have been found in the upper urinary tract. Allopurinol administration predisposes canine patients receiving it to xanthine urolith formation as a result of the drug's inhibition of xanthine oxidase. No medical dissolution protocol exists for xanthine uroliths. The recommended prevention protocol in the dog consists of feeding a protein-restricted, alkalinizing diet such as Hill's Canine k/d®.

Cystine

Cystine uroliths are uncommon in dogs (1% prevalence). Formation of this type of urolith results from an inherited disorder of renal tubular transport that causes cystine and other amino acids to have insufficient reabsorption in the renal tubules. Affected dogs are commonly 4 – 6 years-of-age at the time that cystine uroliths are detected. Affected breeds of dogs include English bulldogs, Newfoundlands, dachshunds, Irish terriers, basset hounds, and bull mastiffs. Male dogs are more commonly affected than female dogs except in the case of the Newfoundland where both sexes seem equally affected. Cystine crystals are large, flat, and hexagonal and form small, spherical uroliths that are light yellow, brown, or green. The observation of cystine crystals should always be considered abnormal. Cystine crystals precipitate out in acid urine, are relatively radiolucent, and commonly require a contrast study or ultrasonography for detection.

An alkalinizing, low protein diet such as Hill's u/d® is recommended for treatment and prevention of cystine uroliths in the dog. A dissolution protocol is available. Thiol disulfide exchange drugs, d-penicillamine(Cuprimine®) and 2-MPG {Thiola® (Tiopronin)}, are used in dissolution. These drugs combine with the precursors of cystine to produce a more soluble product. D-penicillamine is administered at a dose of 15 mg/kg q 12 hrs, and 2-MPG is administered at a dose of 20 mg/kg PO q12 hrs. The thiol disulfide exchange drugs are most effective at a neutral to alkaline pH. The major side effect of d-penicillamine is vomiting, which can usually be managed by giving it with food , using an antiemetic, or decreasing the dose slightly. Side effects do not occur as commonly with 2-MPG administration but can include behavioral changes, myopathy, proteinuria, thrombocytopenia, immune-mediated anemia, skin lesions, lethargy, elevated liver chemistry values, and/or sulfur odor to the urine. Dissolution will be successful in about 2/3 of the dogs treated and requires about 1 – 3 months. The high rate of recurrence of cystine uroliths and the inherited predisposing defect make prevention very important for dogs that have experienced an episode of cystine urolith formation. A prevention protocol consists of administering 2-MPG at a dose of 15 mg/kg q12 hrs PO, adding water to the patient's food, and alkalinizing the urine with potassium citrate at a dose of 100 – 150 mg/kg/day. Sodium bicarbonate may be used as an alternative alkalinizing agent at a dose of 1 gm/5 kg body weight (1/2 tsp baking soda = 2 gm sodium bicarbonate). An alternative prevention protocol calls for feeding Hill's u/d® plus administering 2-MPG or d-penicillamine.

Silicate

Silicate uroliths occur uncommonly in the dog (< 1% of all urolith types(Osborne,2006)) and have a predisposition for the German shepherd and the Old English sheepdog. These uroliths frequently take on a "jackstone" appearance and are grayish white to brown in color. They are radiodense and found most frequently in the bladder and urethra. Silicate uroliths are composed of primarily amorphous silica crystals. No method of medical dissolution is currently available. Surgical removal is usually necessary. Although uncommon, reoccurrence is possible. The etiology 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. No relationship has been established between urine pH and urolith formation. Currently the only recommendations for prevention are to increase water consumption and to avoid diets high in plant proteins.

Recommended Reading:

Bowles, Mary H. Stalking stones: an overview of canine and feline urolithiasis. Veterinary Medicine. October, 2008. Use either of the following computer links:

http://veterinarymedicine.dvm360.com/vetmed/Feline+Center/Stalking-stones-An-overview-of-canine-and-feline-u/ArticleStandard/Article/detail/557955http://dvm360.com(write

or

Google http://dvm360.com → write "urolithiasis" in search engine → click on "Stalking stones: An overview of canine and feline urolithiasis-Veterinary Medicine" entry