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Urate Urolithiasis

Urate and xanthine uroliths belong to the family of naturally occurring purine uroliths. Ammonium urate, a salt of uric acid, is the most common substance in urate uroliths.1 Urate uroliths are the third most common type of urolith in dogs but account for only 5% to 8% of uroliths submitted for analysis.2,3 A genetic predisposition has been docu-mented in dalmatians and is suspected in English bulldogs.1,3 Other breeds re -ported to be overrepresented include the Yorkshire terrier, miniature schnau-zer, shih tzu, and Russian black terrier.3,4 Urate uroliths are also associated with portovascular anomalies, although they can occur with any severe hepatic dys-function.5 Similar to dogs, the prevalence of urate-containing uroliths in cats is low; however, these uroliths constitute the third most common feline urolith type submitted for analysis.6,7 Siamese cats may be predisposed.6,7 The pathogen-esis in cats (with the exception of por-tosystemic vascular anomalies) remains unclear.8

PathogenesisIngested protein and endogenous pro-tein turnover are sources of purines, which are metabolized to hypoxanthine. Through the action of xanthine oxidase, hypoxanthine is converted to xanthine and uric acid (Figure 1). In most mam-mals, uric acid is converted to allantoin by the action of hepatic uricase, and only scant amounts of uric acid are excreted in urine.1 Allantoin is very soluble compared with uric acid.1 Uric acid excreted in the urine may complex with various cations (e.g., ammonium, sodium) to form urate salts. Ammonium is exceptional in its ability to precipitate uric acid in the form of ammonium urate9 (Figure 2). As urine becomes supersaturated with urate salts, urate uroliths may form. Whether uric acid complexes with other substances to form a less soluble salt depends on several factors. Hyper-uricosuria is one factor implicated in the development of urate urolithiasis. Other factors include increased renal excretion or microbial urease production of ammo-

❯❯ John McCue, DVM❯❯ Cathy Langston, DVM,

DACVIM (Small Animal Internal Medicine)

❯❯ Douglas Palma, DVM❯❯ Kelly Gisselman, DVM

Animal Medical Center New York

Pathogenesis Page 468

Diagnosis Page 470

Treatment Page 470

Evaluating Response to Medical Therapy

Page 473

Prevention Page 473

Cats Page 474

At a Glance

Abstract: Urate uroliths belong to the purine family of uroliths and are the third most com-mon urolith type in dogs and cats. In dalmatians, an autosomal recessive trait is respon-sible for hyperuricosuria and a predisposition to urate urolithiasis. In other dog breeds and in cats, urate uroliths are predominantly associated with liver disease, specifically portosystemic vascular anomalies. Idiopathic urate uroliths may occur in animals without liver disease. Ammonium urate uroliths are most common. Urate uroliths are amenable to medical dissolution. This article reviews the pathogenesis and management of urate urolithiasis.

TO LEARN MORE

This article is part of a series on the pathogenesis and treatment of urolithiasis. The first article, “Diagnosis of Urolithiasis” (August 2008), is available on CompendiumVet.com.

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nium ions, aciduria, and the presence of pro-moters (e.g., cellular debris, crystals) or lack of inhibitors (e.g., urinary glycoproteins) of uro-lith formation.1

DalmatiansIt is hypothesized that despite adequate con-centrations of hepatic uricase, dalmatians have a defect in transmembrane transport of uric acid in hepatocytes and renal tubular cells.10 Early studies have shown that the hepatic membrane transport defect plays a significant role in hyperuricosuria in this breed.10 As a result, these dogs have a higher serum con-centration of uric acid, and filtered uric acid is poorly reabsorbed in the renal tubules.10

Although dalmatians exhibit relative hyper-uricosuria, not all form uroliths.1 Urate urolith–forming dalmatians have been shown to excrete higher levels of uric acid in their urine; how-ever, the pathogenesis in urolith-forming dogs is multifactorial.1,6,9–11 Approximately 92% to 97% of the urate uroliths from dalmatians that are submitted for analysis are from male dogs11,12 (Figure 2). The estimated prevalence of urate urolithiasis in male dalmatians ranges from 27% to 34%.13 Differences in anatomy, genetic factors, and urine composition are thought to account for the disparity in incidence between male and female dalmatians. In general, the urethra of female dogs is shorter and wider than that of males, which may allow small stones to be voided before detectable clinical signs develop. In one large, retrospective analysis of breed-related data for stone formation,14 male dalmatians were shown, in general, to have a significantly increased risk of urolith formation compared with females. Differences in the rela-tive levels of inhibitors or promoters of calculo-genesis may also exist between the sexes.15

An autosomal recessive mode of inheri-tance controlled by a single autosomal gene pair (CFA03) was recently demonstrated for hyperuricosuria in dalmatians.16 However, it is not yet clear that this genetic marker will help breeders in identifying urolith-forming dogs.16

Other BreedsIn non-dalmatian breeds, most uric acid is metabolized in the liver to allantoin. The small amount of uric acid that is filtered at the glom-eruli is largely reabsorbed by the proximal

tubules, and trace amounts are excreted in the urine. Relatively little is known about naturally occurring urate urolithiasis in non-dalmatian breeds of dogs.17 Among these, English bull-dogs have the highest incidence.3,18 Mildly elevated serum uric acid levels have been documented in English bulldogs with urate urolithiasis and normal hepatic function.1

Hepatic DysfunctionHepatic insufficiency and portovascular anom-alies can predispose dogs and cats to urate urolithiasis by reducing hepatic conversion of uric acid to allantoin and of ammonia to urea. Urate urolithiasis is a common finding in patients with portovascular anomalies, but it is infrequently associated with hepatic insuf-ficiency due to other causes.5

Dalmatians and English bulldogs have a genetic predisposition to urate urolithiasis.

QuickNotes

Figure 1

Purine metabolic pathway.

Urate Urolithiasis

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DiagnosisClinical SignsClinical signs are usually referable to the level of the urinary tract affected and are indistin-guishable from those of other lower urinary tract disease. Signs consistent with hepatic encephalopathy or liver failure may be noted if urate stones are a consequence of hepatic dysfunction.1,5 The average age at which urate urolithiasis is detected in dalmatians is 4.5 years (range: <1 to 16 years).14

Laboratory EvaluationThe results of a complete blood count and serum biochemical profile are usually nor-mal. Azotemia, metabolic acidosis, and hyperkalemia are common in cases of obstructive uropathy. Changes compatible with concurrent liver dysfunction may be present. Alkaline phosphatase and alanine aminotransferase activities may be normal or increased and albumin and glucose lev-els may be decreased. Increased fasting and postprandial bile acid levels and/or increased plasma ammonia concentrations are concur-rent findings in animals with portovascular anomalies.5 Urinalysis may reveal urate crys-talluria. This finding should be considered abnormal in cats and non-dalmatian dogs1,17; however, urate crystalluria is not synonymous

with urate urolithiasis. The chemical composi-tion of a removed urolith can be confirmed by submission to a reference laboratory for quantitative analysis. Quantitative analysis can provide definitive information about min-eral composition and guide therapy. Reference laboratories should be contacted for specific sample handling and submission instructions. In addition to urinalysis, urine should be sub-mitted for culture to rule out concurrent infec-tion as a complicating factor in management.

ImagingApproximately 97% of urate uroliths are found in the bladder or urethra, with only 3% found in the kidneys or ureters.3 The stones are radio-lucent, usually small (range: <1 mm to 1.5 cm), and round or ovoid. These characteristics lead to a 20% false-negative detection rate with survey radiography.19 Larger stones and those mixed with other components (particularly secondary infection–induced struvite) may be more visible. Double-contrast cystography is the best method for determining the size, shape, and number of stones. This technique has a detection rate of 78% for stones >1.0 mm and allows urethral calculi to be visual-ized.20 Ultrasonography may be used to visu-alize urate uroliths in the bladder or kidney. Ureteroliths often require excretory urography for detection.1,19 TreatmentDietUrate uroliths are often amenable to dissolution through a combination of dietary modification, urine alkalization, and control of second-ary infections (Figure 3). Protein (particularly purine) restriction is the foundation of medical management. Currently, two veterinary diets are marketed for this purpose in dogs. These diets are formulated to maintain alkaline urine. Protein restriction indirectly alters renal medul-lary tonicity by lowering blood urea nitrogen (BUN) content, which limits concentrating abil-ity. Feeding a canned diet or adding water to dry formulations further increases urine volume. Diets severely restricted in protein content are contraindicated in growing or lactating animals. Recipes for homemade diets and modifications of commercially available formulas have been published, but their effectiveness has not been established.1,21

Cystic urate uroliths removed from a 7-year-old castrated dalmatian. Inset: Photomicrograph (400× magnification) of ammonium urate crystals in urine sedi-ment. Note the characteristic brown-gold of ammonium urate crystals in sediment. These crystals are commonly described as having a

“thorn-apple” appearance (black arrow).

Figure 2

Male dalmatians are overrepresented for clinical disease.

QuickNotes

Urate Urolithiasis

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Figure 3

Treatment algorithm for canine urate urolithiasis.

Urate Urolithiasis

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Urine AlkalinizationUrine pH is an important modifier of urate sol-ubility. The optimum target range for urine pH is 7.0 to 7.5.1,8–10,19 Urine pH values >7.5 may pre-dispose dogs to the formation of calcium phos-phate uroliths.1,19 Additional agents are used when optimal urine pH is not achieved with diet alone (Figure 3). Potassium citrate (initial dose: 40 to 90 mg/kg PO q12h) is the preferred agent. Deposition of calcium phosphate over existing uroliths may complicate dissolution. Xanthine oxidase inhibitors are used to decrease uric acid production. Allopurinol, a synthetic isomer of hypoxanthine, is a potent inhibitor of xanthine oxidase22 that inhibits the conversion of hypoxanthine to xanthine and of xanthine to uric acid. Its biotransformation takes place primarily in the liver.22 Allopurinol is poorly bound to plasma proteins and is excreted primarily by the kidneys; therefore, it should be used cautiously in animals with hepatic or renal dysfunction. Its half-life in dogs is approximately 2.5 hours. The bioavail-ability of allopurinol is not affected by food. The initial dose of allopurinol is 15 mg/kg PO bid for 4 weeks, at which time, the size, shape, and number of calculi should be reeval-uated. The level of uric acid excretion in the urine may be used to guide dose adjustments after the first month. Measurement of urinary uric acid excretion over 24 hours (target level: <300 mg urate/24 hr) gives the most accurate value; however, it is difficult to obtain a com-plete 24-hour urine collection.23 Single urinary uric acid:creatinine ratios can be used to doc-ument a decrease in uric acid excretion.24

On average, urate cystoliths dissolve over 3.5 months (range: 1 to 18 months) when a combination of diet, pH modification, and xanthine oxidase inhibition is used.1 In male dogs, dissolving cystoliths may move into the urethra and cause clinical signs of obstruction. Retrograde urohydropropulsion can be used to relieve obstructions.21 Allopurinol should not be used in patients with portosystemic shunts.5 Decreased hepatic metabolism may result in a prolonged half-life and adverse effects, including augmented xan-thine oxidase inhibition that causes xanthine urolithiasis. Allopurinol is also an inhibitor of the hepatic microsomal P450 system and should be used judiciously with other drugs that depend on biotransformation in the liver.25

Adverse effects noted in people include skin rash, gastrointestinal disturbances, thrombo-cytopenia, vasculitis, and hepatitis with other immune-mediated reactions. Many of these reactions were noted in people with existing renal dysfunction.26 There is only one report of potential immune-mediated hemolytic ane-mia and trigeminal neuropathy in a dog.26 Allopurinol should be used only in conjunc-tion with a protein-restricted diet. Excessive purine precursors in the diet may predispose patients to xanthinuria and the formation of xanthine uroliths.27 If xanthine urolithiasis occurs, allopurinol should be discontinued for 1 to 2 months while dietary therapy and urine alkalinization is continued to allow the uro-liths to dissolve. Xanthine exhibits solubility characteristics similar to those of urate in alka-line urine. Following resolution of xanthine urolithiasis, allopurinol can be reintroduced with a 25% reduction in dose. In patients with cystic uroliths that are smaller in diameter than the distended urethra, voiding urohydropulsion or catheter-assisted retrieval may be used to retrieve remaining uroliths and monitor therapy1 (Figure 3).

Infection ControlAny existing urinary tract infection should be eliminated. Infections are generally considered to be secondary to urolith-induced trauma or to catheterization or other invasive procedures.28

Nonmedical ManagementIf medical dissolution is not pursued, surgical and nonsurgical options are available. Surgery is the most definitive method of treatment.1 Surgical attenuation is recommended for defin-itive treatment of identified cystic calculi.5 In patients with portosystemic shunts, correction of the shunt may result in spontaneous disso-lution of urate uroliths if hepatic perfusion is reestablished. If shunt correction is contraindi-cated, dietary management is recommended.5

Voiding urohydropulsion has been described as a means of obtaining stones for analysis and for removing cystic uroliths, when appropri-ate.19 Retrograde urohydropulsion can be used to temporarily relieve any urethral obstruction while a patient is stabilized for surgery.19,a

Urate uroliths are amenable to medical dissolution.

QuickNotes

aVoiding and retrograde urohydropulsion, along with other methods of removing uroliths, will be described in a future article in this series.

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Lithotripsy is a recent addition to the list of management options for urinary calculi in dogs and cats. Shock wave lithotripsy and laser lithotripsy techniques have been described.29–31 Although extracorporeal shock wave lithotripsy (ESWL) is useful in managing nephroliths and ureteroliths, its use for urate uroliths is poorly described, perhaps partly because these uro-liths occur infrequently in the upper urinary tract.29 Successful resolution was achieved in two of five dogs with purine uroliths of the upper urinary tract using ESWL.30 ESWL is not currently recommended for treatment of cystic uroliths in dogs and cats. Laser lithotripsy has been evaluated for the treatment of ureteral, cystic, and urethral uroliths. Laser lithotripsy has become more widely available and may be more practical than ESWL for veterinary patients. When a holmium:YAG laser is used to fragment uro-liths, stone composition does not have a sig-nificant effect on fragmentation time.29 Laser fragmentation of urate uroliths can result in uric acid conversion to cyanide.31 The risk of clinical toxicity is considered to be very low, and laser lithotripsy has been used for urate uroliths without complications.30 As more experience is gained with laser lithotripsy and this procedure becomes more widely available at referral institutions, it may replace other therapies for cystic urate urolithiasis.

Evaluating Response to Medical TherapyPeriodic evaluation is necessary to assess owner compliance and the rate of urolith dis-solution. After the initial enumeration and measurement of uroliths, patients should be reevaluated monthly until uroliths are no lon-ger present. Double-contrast cystography or ultrasonography is usually necessary. Urine pH, specific gravity, and sediment analysis should be evaluated along with BUN to deter-mine the success of medical therapy. If uroliths fail to decrease in size, or if they increase in size during the initial 8 weeks of therapy, the diagnosis should be reevaluated or an alterna-tive management option pursued.1

PreventionThe foundation of preventive therapy is in- creased water consumption and dietary modi-fication (Table 1). The aforementioned pre-scription diets are appropriate for long-term

feeding. Feeding of an exclusively canned diet is recommended. Use of ultralow-pro-tein diets has been associated with dilated cardiomyopathy in English bulldogs and a few dalmatians.32,33 Taurine and/or carnitine deficiency may underlie the development of dilated cardiomyopathy in predisposed dogs.32 Oral taurine supplementation has not been definitively shown to affect outcome.33 It has been suggested that English bulldogs be fed a low-protein renal diet instead of an ultralow-

Table 1 Summary of Urate Prevention StrategiesIntervention Comments Goals

Diet Foundation of all prevention strategies; may be useful as sole therapy

Restricted purine content

Alkalinized urine

Increased water consumption

Allopurinol Use as needed for refractory cases Alkalinized urine

Monitoring Recheck urinalysis and BUN every 4–8 weeks

Urine pH 7.0–7.5

Urine specific gravity <1.020

No urate crystals

BUN <10 mg/dL

If no recurrence for 2–4 months, recheck every 6 months

If uroliths recur, refer to Figure 3

Purine Content of Common Foodsa

High content: foods to avoid Organ meats Fish (salmon, tuna, Shellfish mackerel, sardines)

Moderate content: moderate use Other fish Legumes Spinach Peas Muscle meats Mushrooms

Negligible Breads Fats Cheese Eggs Fruits Carbohydrates Milk Nuts

aNot an all-inclusive list.

box 1

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References1. Bartges JW, Osborne CA, Lulich JP, et al. Canine urate urolithia-sis: etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 1999;29(1):161-191.2. Osborne CA, Lulich JP, Polzin DJ, et al. Analysis of 77,000 ca-nine uroliths. Perspectives from the Minnesota Urolith Center. Vet Clin North Am Small Anim Pract 1999;29:17-38.3. Houston DM, Moore AE, Favrin MG, et al. Canine urolithiasis: a look at over 16,000 urolith submissions to the Canadian Veteri-nary Urolith Centre from February 1998 to April 2003. Can Vet J 2004;45(3):225-230.4. Bende B, Nemeth T. High prevalence of urate urolithiasis in the Russian black terrier. Vet Rec 2004;155(8):239-240.5. Bartges JW, Cornelius LM, Osborne CA. Ammonium urate uroliths in dogs with portosystemic shunts. In: Bonagura JD, ed. Kirk’s Current Veterinary Therapy XIII. Philadelphia: WB Saunders; 2000:872.6. Houston DM, Moore AEP, Favrin MG, et al. Feline urethral plugs and bladder uroliths: a review of 5484 submissions (1998–2003).

Can Vet J 2003;44:974-977.7. Cannon AB, Westropp JL, Ruby AL, et al. Evaluation of trends in urolith composition in cats: 5,230 cases (1985-2004). JAVMA 2007;231:570-576.8. Osborne CA. Diseases of the lower urinary tract. In: Finco DR, Osborne CA, eds. Canine and Feline Urology and Nephrology. Balti-more: Lippincott Williams and Wilkins; 1995:822-833. 9. Sorenson JL, Ling GV. Diagnosis, prevention, and treatment of urate urolithiasis in dalmatians. JAVMA 1993;203(6):863-869.10. Sorenson JL, Ling GV. Metabolic and genetic aspects of urate urolithiasis in dalmatians. JAVMA 1993;203(6):857-862.11. Albasan H, Lulich JP, Osborne CA, et al. Evaluation of the asso-ciation between sex and risk of forming urate uroliths in dalmatians. JAVMA 2005;227(4):565-569.12. Ling GV, Franti CE, Ruby AL, et al. Urolithiasis in dogs I: mineral prevalence and interrelations of mineral composition, age, and sex. Am J Vet Res 1998;59:624-629.

protein diet, with allopurinol administered as needed.34 Allopurinol may be continued as maintenance therapy in cases of recurrent urate urolithiasis. Because of the risk of xan-thine uroliths with long-term administration, regular monitoring is important.1 Despite general hyperuricosuria in dalma-tians, prescription diets may not be indicated in all patients and should be used on an indi-vidual basis.1,8,11,19 Because of the low risk of clinical urate urolithiasis, the rationale for pro-phylaxis in female dalmatians has been ques-tioned.11 The general recommendation is to limit protein sources that are high in purines in this breed19 (box 1). It is suggested that pro-tein consumption be limited to <20% protein on a dry matter basis.1 Given the relatively late onset of clinical signs and multiple factors involved, breeding selection against this trait is difficult.

CatsUrate uroliths are the third most common uro-lith type in cats, accounting for approximately 6% to 9% of feline uroliths submitted for analy-sis.6,7 Unlike struvite and calcium oxalate uro-liths, the incidence of urate uroliths seems to have remained stable over the past 2 decades. In cats, urate uroliths are found almost exclu-sively in the bladder, and males and females are equally affected.7 With the exception of portovascular anomalies, the pathogenesis of urate uroliths in cats is unknown. Screening for occult hepatopathy is recommended in all cats with urate-containing uroliths.8,34 Suggested risk factors in cats include the formation of highly acidic, highly concentrated urine asso-

ciated with diets high in purine precursors.8 Surgery remains the treatment of choice in cats, as medical dissolution protocols have not been developed for this species. Additional stud-ies of the efficacy and safety of allopurinol in cats are needed. Successful dissolution has been noted only anecdotally. Any concurrent infec-tions should be treated based on culture and sensitivity testing. Prevention is similar to that in dogs and is centered on feeding a low-protein diet, limited in purine precursors, that promotes formation of moderately dilute urine of neutral pH.14 There is no feline equivalent of the canine prescription diets; however, prescription feline diets for the management of renal disease have been used with success. Many of these diets are formulated with potassium citrate. Prevention of recurrence was noted to be >90% with one such diet.34 The addition of supplemental potassium citrate can be used to achieve an appropriate urine pH.

ConclusionUrate and xanthine uroliths are generally uncom-mon, except in dalmatians. Ultrasonography and double-contrast cystography are the best imag-ing techniques for diagnosing these radiopaque calculi. The presence of urate uroliths or crystal-luria in a breed that is not predisposed should prompt evaluation for a portosystemic shunt. Urate uroliths are generally small and may be removed by dissolution, nonsurgical, or surgical techniques. Purine- and protein-restricted diets that alkalinize the urine are recommended for dissolution, as well as for prevention in male dalmatians. Allopurinol is used in some cases to aid dissolution and prevention.

Urate uroliths are radiolucent on survey radiographs.

QuickNotes

Urate Urolithiasis

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1. A genetic predisposition for urate uro­lith formation is suspected in

a. Yorkshire terriers. b. shih tzus. c. English bulldogs. d. miniature schnauzers.

2. The major excretory end product of purine metabolism in dogs and cats is

a. xanthine. b. allantoin. c. uric acid. d. ammonia.

3. The suspected mechanism of hyper­uricosuria in dalmatians is

a. congenital uricase deficiency. b. portosystemic vascular anomaly. c. transmembrane transport defect of

hepatocytes and renal tubular cells. d. recurrent urinary tract infection.

4. The target urine pH for prevention of urate crystallization is

a. <6.5. c. 7.0–7.5. b. 6.6–7.0. d. >7.5.

5. A predisposition for formation of urate uroliths is suspected in _______ cats.

a. Siamese b. Persian c. Himalayan d. Abyssinian

6. What percentage of urate uroliths are found in the upper urinary tract?

a. 3% c. 8% b. 5% d. 20%

7. Which parameter is not useful when evaluating response to medical therapy for urate urolithiasis?

a. serum BUN b. urine sediment c. survey radiographs d. urine pH

8. The detection rate of urate urocystoliths using double­contrast cystography is _______ for stones >1.0 mm.

a. 65% c. 85% b. 78% d. 100%

9. _______ is a recognized side effect of allopurinol therapy in dogs.

a. Pyoderma b. Liver failure c. Xanthine urolithiasis d. Thrombocytopenia

10. Use of ultralow­protein diets formu­lated for prevention of urate urolithia­sis is implicated in the development of _______ in predisposed English bulldogs.

a. dilated cardiomyopathy b. liver failure c. renal disease d. xanthine urolithiasis

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13. Bannasch DL, Ling GV, Bea J, et al. Inheritance of urinary calculi in the dalmatian. J Vet Intern Med 2004;18:483-487.14. Ling GV, Franti CE, Ruby Al, et al. Urolithiasis in dogs II: breed prevalence and interrelations of breed, sex, age, and mineral com-position. Am J Vet Res 1998;59(5):630-642.15. Carvalho M, Lulich JP, Osborne CA, Nakagawa Y. Role of uri-nary inhibitors of crystallization in uric acid nephrolithiasis: dalma-tian dog model. Urology 2003;62(3):566-570.16. Safra N, Schaible RH, Bannasch DL. Linkage analysis with an interbreed backcross maps dalmatian hyperuricosuria to CFA03. Mamm Genome 2006;17(4):340-345. 17. Kruger JM, Osborne CA. Etiopathogenesis of uric acid and am-monium urate uroliths in non-dalmatian dogs. Vet Clin North Am Small Anim Pract 1986;16:87-126.18. Bartges JW, Osborne CA, Lulich JP, et al. Prevalence of cysteine and urate uroliths in bulldogs and urate uroliths in dalmatians. JAVMA 1994;204(12):1914-1918.19. Adams LG, Syme HM. Canine lower urinary tract diseases. In: Ettinger SJ, Feldman E, eds. Textbook of Veterinary Internal Medi-cine. Philadelphia: WB Saunders; 2006:1850-1874.20. Weichselbaum RC, Feeney DA, Jessen CR, et al. Urocytolith detection: comparison of survey, contrast radiographic and ultra-sonographic techniques in an in vitro bladder phantom. Vet Radiol Ultrasound 1999;40(4):386-400.21. Osborne CA, Bartges JW, Lulich JP, et al. Canine urolithiasis. In: Hand MS, Thatcher CD, Remillard RL, et al, eds. Small Animal Clini-cal Nutrition. 4th ed. Topeka: Mark Morris Institute; 2000:605-688.22. Hande K, Reed E, Chabner B. Allopurinol kinetics. Clin Pharma-col Ther 1978;23(3):598-605.23. Bartges JW, Osborne CA, Felice CJ, et al. Reliability of single

urine and serum samples for estimation of 24-hour urinary uric acid excretion in six healthy beagles. Am J Vet Res 1994;55:472-476.24. Moentk JA, Dibartola SP, Buffington CA. Effect of allopurinol on urine urate-to-creatinine rations in normal dalmatians. JAAHA 1994;30:483-486.25. Vessell ES, Passananti GT, Greene FE. Impairment of drug me-tabolism in man by allopurinol and nortriptyline. New Engl J Med 1970;313:1484-1499.26. Pedroia V. Allopurinol-induced immune disorders. Canine Pract 1980;8:19-22.27. Bartges JW. Canine xanthine uroliths: risk factor management. In: Kirk RW, Bonagura JD, eds. Kirk’s Current Veterinary Therapy IX. Philadelphia: WB Saunders; 1992:900-905.28. Lees GE. Bacterial urinary tract infections. Vet Clin North Am Small Anim Pract 1996;26:297-304.29. Davidson EB, Ritchey JW, Higbee RD, et al. Laser lithotripsy for treatment of canine uroliths. Vet Surg 2004;33:56-61.30. Adams LG. Lithotripsy using shockwaves and lasers. Proc 24th Annu ACVIM Forum 2006:439-441. 31. Teichman JM, Vassar GJ, Glickman RD, et al. Holmium:YAG lithotripsy: photothermal mechanism converts uric acid calculi to cyanide. J Urol 1998;160:320-324.32. Freeman LM, Mitchel KE, Brown DJ, et al. Idiopathic dilated cardiomyopathy in dalmatians: nine cases (1990-1995). JAVMA 1996;209(9):1592-1596. 33. Freeman LM, Rush JE, Brown DJ, et al. Relationship between circulating and dietary taurine concentrations in dogs with dilated cardiomyopathy. Vet Ther 2001;2(4):370-378.34. Bartges J, Kirk C. Nutrition and urolithiasis. Proc 25th Annu ACVIM Forum 2007:13-15.