Feline uroliths (Proceedings)

Urolithiasis is common in the cat, causing morbidity and, occasionally, mortality. Diagnosis is based on clinical signs, imaging, gross physical characteristics of the uroliths, and quantitative analysis of the urolith. Therapy depends upon urolith composition and associated etiology as well as location of the urolith in the urinary tract. It should be remembered that increasing water intake is essential in the treatment and prevention of all uroliths regardless of composition. The following discussion covers many of the urolith types found in the cat.

Struvite

The struvite (magnesium ammonium phosphate hexahydrate) urolith is one of the most common uroliths occurring in the cat. A study at the Minnesota Urolith Center analyzing feline uroliths from 1981 – 2002 revealed a change in the status of struvite urolith prevalence.(Osborne,2006) In 1981 uroliths composed of struvite represented the overwhelming majority of feline uroliths (78%), but a steady decline was seen over a period of several years with struvite decreasing to a prevalence of approximately 33%. Beginning in 2003 the frequency of feline struvite uroliths began to notably increase, reaching a level of 48.1% in 2005 and again establishing struvite as the most prevalent feline urolith composition identified at the Minnesota Urolith Center. A separate California study analyzing a large number of uroliths over a similar time period supports the trend in recent increases in feline struvite uroliths.(Cannon,2007) The shift in urolith prevalence in the cat 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. However, this theory does not seem to explain the fact that during the same 25-year time period, the mineral composition of feline urethral plugs has remained consistently and overwhelmingly struvite (87% in 2005).(Osborne, 2006)

Occasionally calcium phosphate and calcium carbonate phosphate will also be associated with struvite uroliths. Struvite uroliths vary greatly in size, ranging from sand-like particles to specimens well over 1 cm in diameter. Struvite uroliths are generally sufficiently radiodense to be seen easily on survey films. These uroliths assume a variety of shapes, but are often spherical or pyramidal (flat-sided). Uroliths that have a pyramidal shape or that are > 1 cm in diameter are most often of struvite origin. In some cases a struvite urolith will take on the shape of the portion of the urinary tract surrounding it. Struvite crystals precipitate out more readily in alkaline urine and have an angular, prism-like appearance.

Struvite uroliths can either be infectious or sterile in origin. Infection-related uroliths occur more commonly in cats < 1year-of-age and > 10 years-of-age. The majority of feline struvite uroliths are sterile and are not associated with a known sex predisposition. Feline breeds predisposed to struvite formation include the foreign shorthair, ragdoll, Chartreux, Oriental shorthair, domestic shorthair, and Himalayan. The age predisposition for sterile struvite urolith formation in the cat is between 1 and 10 years-of-age with the incidence decreasing after approximately 7 years-of-age.

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

Feeding a calculolytic diet such as feline Hill's s/d® can dissolve both sterile and infection-related struvite urocystoliths and nephroliths, by creating an acidic, dilute urine undersaturated with magnesium, and ammonium. The time for urolith dissolution is variable, but averages about 2 - 3 months for infection-related uroliths and 3 – 6 weeks for sterile uroliths. 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. Diagnostic imaging is the primary means of determining the success of the dissolution therapy. 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. . 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 restrictions and increased sodium content of Hill's s/d® make it unsuitable as a diet for or kittens, pregnant pets, or lactating pets.

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 feline Control Formula®). Hill's feline w/d® can be used in struvite prevention programs when patient obesity is a concern. Preventative diets for sterile struvite uroliths are less restrictive than the calculolytic diets, but are still not satisfactory for kittens, 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

Over much of the last three decades the prevalence of calcium oxalate uroliths in the cat has steadily increased as the prevalence of struvite uroliths has decreased. However, in the past decade, that trend has been reversed as calcium oxalate urolith numbers have declined while uroliths of struvite composition have increased. In 2005 the Minnesota Urolith Center reported calcium oxalate as the second most prevalent type of feline urolith with an incidence of 40.6%. A male gender predisposition for calcium oxalate urolith formation has been recognized in the cat. Older cats (bimodal peaks at 5 and 12 years of age) have been found to have the greatest risk for developing calcium oxalate uroliths. Breed predispositions have also been recognized, including the ragdoll, British shorthair, foreign shorthair, Himalayan, Havana brown, Scottish fold, Persian, and exotic shorthair. Cats housed indoors may be at greater risk for developing calcium oxalate uroliths, which could be a consequence of a decrease in both water consumption and voiding.

Calcium oxalate uroliths are very radiodense and usually readily seen on survey films. This type of urolith varies in both size and shape, sometimes taking on a very smooth appearance and other times assuming a very jagged "roserock" appearance. Calcium oxalate uroliths are made up of two different types of crystals, monohydrate and dihydrate. Calcium oxalate uroliths composed predominately 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 those uroliths composed predominately of dihydrate crystals, which have a classic "maltese cross" appearance and are more likely to produce a urolith that has an irregular surface. Calcium oxalate crystals precipitate out more readily in urine with an acidic pH.

Hypercalcemia is a predisposing factor for calcium oxalate urolith formation and has been reported to occur in 35% of cats with this type of urolith.(Hostutler,2005) The hypercalcemia observed in this population of cats usually falls in the idiopathic category. Hypercalciuria contributing to calcium oxalate formation may also occur in some cats 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 or medication can diminish the risk for development of calcium oxalate uroliths.

Treatment of calcium oxalate uroliths is limited to surgical removal, voiding urohydropropulsion, and lithotripsy since no method of medical dissolution of this type of urolith is available. 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. Taking preventative steps is especially desirable since calcium oxalate uroliths have a high rate of recurrence. Many conflicting factors have been reported in regard to the most desirable diet for calcium oxalate prevention. The factors most consistently recommended for prevention include protein restriction, alkalinization, and oxalate restriction. In cats diets formulated for calcium oxalate prevention include Hill's c/d® Multicare and Royal Canin's Urinary s/o®. Hill's feline w/d® plus potassium citrate (75 mg/kg PO q12 hrs) can also be fed, especially to obese patients, and has the added benefit of helping to normalize calcium levels in some hypercalcemic cats with calcium oxalate uroliths. The alkalinizing effect of potassium citrate helps to decrease bone release of calcium and promote excretion of calcium in the more soluble form of calcium citrate. The desired urine pH range for prevention of calcium oxalate formation is 6.5 – 7.5. If dietary measures ± potassium citrate fail to prevent recurrence of calcium oxalate uroliths, the addition of thiazide diuretics (hydrochlorothiazide, 2 – 4 mg/kg PO every 12 hours) to the prevention regimen may be considered in an attempt to decrease the excretion of calcium in the urine. Thiazide diuretics are contraindicated in hypercalcemic patients since the use of this medication could aggravate the hypercalcemic condition. Loop diuretics such as furosemide should be used 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. Supplementation of vitamin C, an oxalate precursor, and vitamin D, an aid to the gastrointestinal absorption of calcium, should be avoided in patients with calcium oxalate urolithiasis.

Purine (Urate, Xanthine)

The third most common non-compound type of urolith reported in the cat is of purine origin, specifically urate. Unlike uroliths of struvite and calcium oxalate composition, urate uroliths have varied relatively little in incidence over the last 20 years, accounting for approximately 4.6% of uroliths in cats. No sex or breed predisposition has been established for urate urolith formation in the cat. The formation of urate uroliths in many cats is considered idiopathic. Some cats can be at risk for developing urate uroliths as a result of metabolism changes related to hepatic disease, especially portovascular anomalies. Although urate uroliths generally occur in cats < 4 years old, urate uroliths associated with portovascular anomalies are frequently found in cats < 1 year old. 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, brown, or green, radiolucent uroliths that are found most frequently in the bladder or urethra. Identifying the presence of this type of of urolith generally requires contrast radiography or high speed ultrasonography.

Allopurinol (7.5 mg/kg PO q12 hrs), a competitive inhibitor of the enzyme xanthine oxidase, and feline Hill's k/d® can be used in a dissolution protocol for the cat. Feeding a feline renal diet such as k/d® is also desirable when administering allopurinol to prevent xanthine urolith formation. The time required for urolith dissolution averages about 3 – 4 months. However, feline urate uroliths, including urate uroliths associated with portosystemic shunts, often cannot be successfully medically dissolved. Consequently, voiding urohydropropulsion, lithotripsy, or surgical intervention is often required to remove urate uroliths in cats. Urinary tract infection occurs commonly with urate uroliths and should be treated with appropriate antibiotics.

Prevention of urate uroliths in cats is generally successful by feeding a renal failure type diet such as feline Hill's k/d®, which is alkalinizing and protein-restricted. 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 recognized more recently in the cat. A familial or congenital defect in the activity of xanthine oxidase is suspected to be the primary cause of feline xanthine urolith formation. Xanthine uroliths are usually a few mm in diameter, have a smooth surface, and are generally yellow, tan, or light brown in color. The urine in affected cats may be a mustard yellow 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. 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. An incidence of 0.1% for feline xanthine uroliths was reported by the Minnesota Urolith Center in 2006. Although allopurinol administration predisposes pets to xanthine formation, most affected cats have not received this drug. No medical dissolution protocol exists for this urolith type. The recommended prevention protocol consists of feeding a protein-restricted, alkalinizing diet such as Hill's Feline k/d®

Cystine

Uroliths of cystine composition are uncommon in cats (<1% prevalence). Cystine urolith formation results from an inherited disorder of renal tubular transport that causes cystine and other amino acids to have insufficient reabsorption in the renal tubules. Male and female cats appear to be equally affected and are diagnosed at a mean age of 4.1 years. The domestic shorthair and Siamese are the cat breeds most commonly affected. Cystine crystals are large, flat, and hexagonal. The observation of cystine crystals should always be considered abnormal. Cystine crystals precipitate out in acid urine to form uroliths that are small, spherical, and light yellow, brown, or green in color. These uroliths are relatively radiolucent and commonly require a contrast study or ultrasonography for detection.

No proven cystine urolith dissolution protocol is available for cats. Elimination of cystine uroliths is accomplished by surgical removal, lithotripsy, or voiding urohydropropulsion. Although the incidence of this type of urolith is the cat is low, the recurrence rate in affected cats appears high. An alkalinizing renal failure diet such as canned or moistened dry feline Hill's k/d® is recommended for prevention of cystine uroliths in the cat.

Dried Solidified Blood (DSB) Uroliths

The DSB urolith is a category of urolith composition recognized more recently in the cat. 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. DSB uroliths appear to be formed from organic material, are generally radiolucent, and are not identifiable by ultrasonography. Contrast radiography may suggest urinary tract obstruction but not reveal a discrete urolith. Domestic shorthair and longhair cats are most commonly affected. No known sex predisposition has been identified. The mean age of cats with DSB uroliths in a report of 49 affected cats was 9 years.(Westropp,2006) No medical dissolution or prevention protocols are currently available. Due to the difficulty in identifying the DSB 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 by methods such as feeding canned food is encouraged.

Compound

Uroliths of compound composition have a center which is at least 70% one mineral type and an outer layer which contains at least 70% of another mineral type. The prevalence of compound uroliths has been reported as < 5% in cats.(Osborne,2006) Quantitative analysis is especially important in selecting appropriate treatment and prevention options when dealing with compound uroliths since the two primary mineral types may have conflicting treatment protocols.

Nephroliths and Urethroliths

Although the majority of uroliths in the cat are found in the bladder or urethra, uroliths are also occasionally located in the pelvis of the kidney or in a ureter. Upper urinary tract uroliths are most commonly of struvite or calcium oxalate composition with calcium oxalate being the most prevalent of the two types. In cases where nephroliths or ureteroliths are suspected to be primarily struvite, medical dissolution can be attempted provided an emergency circumstance does not exist precluding that option. Medical dissolution of ureteroliths is unlikely due to inconsistent exposure of the urolith to urine undersaturated with the minerals forming struvite. Surgical intervention or lithotripsy are the primary options for therapy when the upper urinary tract urolith is suspected to be of calcium oxalate composition and warrants removal. Ureteroliths will sometimes pass on into the bladder or move retrograde into the kidney pelvis. In some cases, ureterolith passage into the bladder can be facilitated by use of smooth muscle relaxants such as prazosin (Minipress® - 0.25 - 0.5 mg/cat q12 hrs PO), fluid therapy, and diuretics. Removing an affected kidney and ureter can be considered if function is severely impaired due to a nephrolith and the other kidney is functioning adequately. Removing a urolith through surgical incision of the renal pelvis or the ureter is also an option, but it must be kept in mind that such procedures can cause permanent damage to these organs. The introduction of a percutaneous approach to surgical incision of the kidney (PCNL) for the purpose of urolith extraction, lithotripsy, or ureteral stent placement holds promise for decreasing the amount of associated damage to the affected area. 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, monitoring the patient's status by evaluating biochemistry profiles, urinalyses, and abdominal imaging periodically, observing for progressive clinical signs, providing pain management as needed, and implementing a preventative plan appropriate for the suspected urolith type is often the best option.