Urolithiasis in Dogs

Astrid Hoppe, DVM, PhD

ABSTRACT

The incidence of clinically significant uroliths is increasing in dogs.The forma-

tion and composition of uroliths may be influenced by a variety of factors,
including species, breed, sex, age, diet, anatomical abnormalities, urinary tract
infection, medication, and urine pH. Confirmation of the diagnosis may require
urinalysis, quantitative urine culture, ultrasonography, and radiography. Non-
specific therapy includes augmentation of water consumption; specific therapy
is based on the urolith composition. Nephroliths are commonly composed of
calcium oxalate; these stones usually require surgical removal. Struvite is one
of the most common minerals found in canine uroliths; one prerequisite for
their formation is oversaturation of the urine with magnesium ammonium
phosphate. Calcium oxalate uroliths, the most common type in humans, are
becoming increasingly prevalent in dogs. Cystinuria is an inborn metabolic dis-
ease characterized by excessive urinary excretion of cystine and the dibasic
amino acids lysine, arginine, and ornithine; the exact mechanism of cystine
urolith formation is unknown. Urate uroliths, which are relatively uncommon
in dogs, typically comprise ammonium acid urate (also known as ammonium
urate), although some may be composed of sodium acid urate and uric acid.

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Urolithiasis
Astrid Hoppe, DVM, PhD,
Diplomate ECVIM-CA
Department of Small Animal

in Dogs
Clinical Sciences, PO Box 7037,
Swedish University of Agricultural
Sciences,
S-750 07 Uppsala, Sweden

The incidence of clinically significant uroliths is increas- vent recurrence depends on the type of urolith, and analy-
ing in dogs. A study of dogs admitted to veterinary col- sis is thus the cornerstone to formulation of urolith man-
leges in North America between 1980 and 1995 found agement.Although simple qualitative chemical analyses are
that lower urinary tract diseases were diagnosed in 3% of commonly used to identify the mineral composition of
dogs (24,087 of 809,849). Of these 24,087 dogs, urolithi- calculi, they are best avoided as both false-positive and
ases were diagnosed in 21.3% of the cases.1 The study false-negative results are common. Quantitative analyses
found that females had a slight but statistically significant performed by qualified laboratories are recommended.
higher risk of lower urinary tract disease than males. Non-specific therapy to prevent recurrence should
Urolithiasis, however, predominated in males (63%) com- include augmentation of water consumption.Animals that
pared with females (37%). In Europe, no precise epidemi- consume additional water will be less likely to form high-
ological data are available. However, the prevalence of ly concentrated urine, and, as a result, the urine will con-
urolithiasis in a German study in the 1980s was 1% to 3%, tain lower concentrations of calculogenic minerals. This
judged by the numbers of cases treated, and the incidence will in turn minimize formation of crystals and uroliths.
was estimated as 0.3% to 0.8%.2 This type of therapy is effective, inexpensive, and safe.The
The incidence and composition of uroliths may be most practical solution to promoting increased water
influenced by a variety of factors including species, breed, consumption is to feed canned diets, which contain 70%
sex, age, diet, anatomical abnormalities, urinary tract to 80% water. If required, additional water can be added
infection, medication, and urine pH. Experience from to the canned food. Strive to maintain a specific gravity of
treatment of geriatric dogs in the USA with lower urinary less than 1.020. Sodium supplements should be avoided—
tract disease showed that urolithiasis increased with studies in both dogs and humans have shown that con-
advancing age up to 15 years.1 Dogs older than 15 years sumption of high levels of sodium increases the renal
had a marked decrease in the frequency of urolithiasis. excretion of calcium and cystine.1,3
Uroliths may be found throughout the urinary pathway Given that effective specific medical treatment of
and may occur on more than one site.The majority found urolithiasis is dependent on a good “guestimation” of
in dogs, however, have been in the lower urinary tract. urolith composition, protocols that allow an estimation of
Ureteral uroliths are uncommon in dogs and usually orig- urolith composition should be formulated (Box 1).
inate in the renal pelvis. Urethral uroliths originate from
the urinary bladder. NEPHROLITHS
Nephroliths are uroliths located in the renal pelvis and/or
UROLITH DIAGNOSIS AND THERAPY collecting diverticula of the kidney. Although they com-
Uroliths are usually suspected on the basis of typical find- prise only approximately 1% to 4% of all uroliths,
ings obtained by history and physical examination. Urinal- nephroliths are an important clinical problem in dogs
yses, quantitative urine culture, ultrasonography, and radi- because of their potential complications. They may
ography are often required to confirm urolithiasis and to obstruct the renal pelvis or ureter, predispose to
determine if uroliths are associated with predisposing dis- pyelonephritis, or result in compressive injury to renal
orders of the urinary tract. parenchyma leading to renal failure. Recurrence is also a
The four most common minerals found in canine frequent problem.
uroliths are magnesium ammonium phosphate (struvite), Nephroliths in dogs most commonly consist of calcium
oxalate, cystine, and ammonium urate. Less common types oxalate.4 This stone type is not amenable to current dis-
of uroliths are calcium phosphate, silica, carbonate, xan- solution protocols and must be surgically removed.
thine, drugs, and drug metabolites. Specific therapy to pre- Because nephrotomy results in reduced renal function,

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BOX 1 urease
NH2 – CO – NH2 + H2O 2NH3 + CO2
Checklist of factors that may aid in
“estimation” of mineral composition
of canine uroliths Further hydrolysis yields:

NH3 + H2O NH4+ + OH –

1 Breed and sex of the dog
2 Quantitative analysis of uroliths from earlier urolith CO2 + H2O H2CO3 H + HCO3–
operations or uroliths passed during micturition
2–
3 Radiographic density of uroliths HCO3– H+ + CO3
Struvite ++ to ++++
Oxalate ++++ Figure 1
Cystine + to ++ Bacterial urease hydrolyzes urea, leading to increased urinary concentration
Calcium phosphate ++++ of ammonium and carbonate and subsequent formation of struvite and
carbonate apatite.
Ammonium urate 0 to ++
Silica ++ to ++++
4 Urine pH
erals found in canine uroliths. Reports from the University of
Struvite and calcium apatite Usually alkaline
Ammonium urate Acid or neutral California at Davis in 1995 showed that approximately 66% of
Cystine Acid canine uroliths were partially or entirely composed of struvite.
Calcium oxalate Variable In Sweden, of 3366 uroliths analyzed in 1990–1997, 43% were
Silica Acid or neutral composed of struvite (Frank, unpublished data). Pure struvite
5 Identification of crystals in the urine sediment. uroliths are uncommon because most struvite calculi contain a
However, only cystine crystals are pathognomonic for small quantity of calcium phosphate and, occasionally, ammoni-
a disease (cystinuria) usually leading to urolith um urate.
formation Oversaturation of urine with magnesium ammonium phos-
6 Type of bacteria, if any, isolated from urine: phate is a prerequisite for struvite urolith formation (Figure 1),
Urease-producing bacteria (staphylococci and Proteus but several factors—including urinary tract infection, alkaline
spp.) are typically associated with struvite uroliths urine, diet, and genetic predisposition—may influence forma-
Urinary tract infection is often absent in patients tion. Of these, urinary tract infection appears to be the most
with calcium oxalate, cystine, ammonium urate, and significant in dogs.
silica uroliths In a small percentage of dogs with struvite urolithiasis, some
7 Hypercalcemia may be associated with calcium- investigators have found both urine and the inside of uroliths
containing uroliths to be sterile.6 Several observations suggest that dietary or
8 The cyanide-nitroprusside test should be performed if metabolic factors may be involved in the formation of such
cystine uroliths are suspected23 uroliths. Pilot studies of clinical cases have revealed dogs with
frequently alkaline urine but without identifiable bacteria and
no detectable urease. However, the pathogenesis of sterile
repeated nephrotomies for recurrent nephrolithiasis may result struvite urolith formation is still unclear. Some information
in progressive loss of renal function and renal failure. Extracor- about the pathogenesis of struvite-containing urolithiasis in
poreal shock-wave lithotripsy (ESWL) should therefore be con- dogs has been elucidated, but the mechanisms of stone accre-
sidered. The safety and efficacy of ESWL for the treatment of tion and dissolution are not fully understood.
spontaneous canine nephrolithiasis and ureterolithiasis has Our clinical experience at the Swedish University of Agri-
been described by various authors, with no significant compli- cultural Sciences, as well as that from other investigators, is
cations reported during treatment.4,5 In one of the studies, 14 that struvite uroliths can form within a month of infection of
of 16 dogs (88%) were either freed completely of their the urinary tract with urease-producing staphylococci. The
nephroliths or had “clinically insignificant renal fragments” and uroliths also tend to recur following surgical removal or med-
were considered successful.4 ical dissolution. All breeds can be affected, but the uroliths are
more often found in females than in males. Uroliths do not
STRUVITE UROLITHIASIS usually form in puppies, although infection-induced struvite
Etiopathogenesis uroliths have been detected in puppies as young as 21⁄2 weeks
Struvite (MgNH4PO4*6H2O) is one of the most common min- (Hoppe, unpublished data).

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■ To increase the solubility of crystalloids in urine, which can

be accomplished by administration of urine acidifiers.
■ To eradicate or control urinary tract infection. Because of
the quantity of urease produced by bacterial pathogens, it
may be impossible to acidify urine.Therefore, sterilization of
urine with appropriate antimicrobial agents is an important
objective in decreasing the concentration of struvite crys-
tals, thereby preventing further growth of the uroliths or
even promoting their dissolution.
■ To decrease the concentration of crystalloids in urine by
stimulation of thirst, thereby increasing urine volume.
■ To reduce the quantity of calculogenic crystalloids in urine;
change in diet is an example of this method.
Figure 2
Struvite urolith from a dog. Dietary considerations
Calculolytic diets have been formulated to reduce urine concen-
tration of urea (which is the substrate of urease), phosphorus, and
Characteristics magnesium.These diets contain a reduced quantity of high-quality
Struvite uroliths are white or pale yellow (Figure 2) and are protein and reduced quantities of phosphorus and magnesium and
predominantly found in the bladder from where they often are supplemented with sodium chloride to stimulate thirst. The
pass into the urethra. They may be present singly or in large efficacy of the diets in inducing urolith dissolution has been con-
numbers, grow rapidly, and sometimes become rather large in firmed by controlled experimental and clinical studies in dogs.8,9
size. Response to therapy should be evaluated every fourth
Analyses in the USA have identified four textural types of week, with dissolution or growth of uroliths measured radio-
struvite uroliths and four textural types of struvite-apatite graphically. Antibiotic therapy should be maintained until
uroliths.7 The authors concluded that the presence of small, urolith dissolution occurs, which can take from 1 to 6 months.9
well-interconnected primary pores in struvite-containing uri- Less time is usually required to induce dissolution of sterile
nary uroliths from dogs appears to be a significant factor in struvite than of infection-induced struvite.
determining the interactions that take place between the Given that calculolytic diets are restricted in protein and
urolith and changes in the urine composition.The progress of supplemented with sodium chloride, they should not be given
dissolution from the surface to the interior of the urolith to patients with heart failure, nephrotic syndrome, or hyper-
appears to be largely affected by the primary porosity original- tension or to growing dogs.10
ly present between crystals forming the urolith framework.
Apatite was observed to be more resistant to dissolution than CALCIUM OXALATE UROLITHIASIS
struvite. The prevalence of fine concentric laminations with Etiopathogenesis and prevalence
low porosity and the common occurrence of apatite in stru- Calcium oxalate uroliths are the most common type in humans
vite uroliths in dogs may be two reasons why the efficacy of in Western countries. Earlier studies showed this type of
dietary and medical manipulations is greater in cats than in urolith to be less common in dogs, representing only 3% to
dogs. 10% of those found.2,11,12 Recent investigations, however, have
shown that uroliths composed primarily of calcium oxalate are
Treatment and prevention increasing in number, accounting for as many as 25% of canine
Management of struvite urolithiasis includes: uroliths submitted for analysis at the University of Minnesota
Urolith Center.13 This is in agreement with the author’s clinical
■ relief of obstruction to urine outflow if necessary experience in Sweden, where calcium oxalate today accounts
■ elimination of existing uroliths for about 43% of uroliths found in dogs.
■ eradication of urinary tract infection Factors incriminated in the etiopathogenesis include hyper-
■ prevention of recurrence of uroliths. calciuria and hyperoxaluria, of which hypercalciuria is probably
the most important predisposing factor in dogs as well as in
Medical dissolution humans. Most of the information concerning calcium oxalate
The objectives and current recommendations of medical treat- uroliths comes from extrapolation of data in humans. Caution
ment of uroliths are: is therefore necessary when using this information in dogs.

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associated with nephroliths and ureteroliths are indications for

surgical removal. For those patients in which surgery is not
indicated, the clinical status of uroliths should be serially
assessed by urinalyses, renal function tests, and/or radiography
or ultrasonography.

Medical treatment and prevention

Following urolith removal, medical protocols should be con-
sidered to minimize recurrence or to prevent growth of
uroliths remaining in the urinary tract (Box 2). In general, med-
ical treatment should have the initial goal of reducing the urine
concentration of calculogenic substances. Caution must be
exercised to ensure that the side effects of treatment are not
Figure 3 more detrimental than the effects of uroliths.
Calcium oxalate uroliths can range from fractions of a millimeter to several
centimeters in size. Dietary considerations
Although there is agreement that excessive consumption of
Normocalcemic hypercalciuria is thought to be the most calcium and oxalate should be avoided, it is not advisable to
common finding in humans, has also been encountered in dogs restrict dietary calcium unless the dogs have absorptive hyper-
with calcium oxalate uroliths, and results from either intestinal calciuria. Even then, only moderate restriction is recommend-
hyperabsorption of calcium or decreased renal tubular reab- ed to prevent negative calcium balances and increased intesti-
sorption of calcium. In contrast, hypercalcemic hypercalciuria nal oxalate absorption.
results from an increased glomerular filtration of calcium, but As far back as the 1930s, it was thought that a magnesium-
this is a relatively infrequent cause of calcium-containing poor diet could enhance the formation of uroliths, an obser-
uroliths in dogs. Potential causes of hypercalcemia include pri- vation that has been occasionally confirmed by later authors. It
mary hyperparathyroidism, pseudohyperparathyroidism, malig- has also been shown that magnesium deprivation leads to
nant lymphoma, and hyperthyroidism. nephrocalcinosis in rats. However, no controlled clinical trials
have investigated dietary magnesium intake in dogs with recur-
Characteristics and detection rent urolithiasis.
Calcium oxalate crystals form in urine as calcium oxalate Moderate dietary restriction of sodium is recommended in
monohydrate or calcium oxalate dihydrate. Urinalysis may patients with active urolith formation, as consumption of high
reveal these crystals, but they may be absent. Determination of levels of sodium increases the renal excretion of calcium.13
serum calcium as well as parathormone concentrations may Human studies indicate that sodium intake probably affects
help to elucidate the underlying mechanism of the disease. Cal- lithogenic mechanism by reducing citrate excretion.16 Reduc-
cium oxalate uroliths are more commonly found in males tion in dietary phosphorus is known to increase hypercalciuria
(approximately 70%) than females and mostly in older dogs.14 due to activation of vitamin D, with a subsequent increased
They may be detected anywhere in the urinary tract, are very intestinal calcium absorption.10 Phosphorus should therefore
radio-dense, and may vary in size from fractions of a millime- not be restricted.
ter to several centimeters (Figure 3). Recurrence is common: Dietary intake of vitamins is often indicated as a lithogenic
In some investigations, uroliths recurred in up to 50% of dogs risk factor. Certain authors have suggested a lack of vitamin A
within 3 years of surgical removal.13 or vitamin B6 as risk factors.17,18 In humans, it is commonly
believed that the high doses of vitamin C may enhance litho-
Therapeutic considerations genesis through increased oxalate excretion. Recent studies,
In contrast to struvite, urate, and cystine uroliths—which dis- however, concluded that the administration of megadoses of
solve when urine is no longer supersaturated with calculogenic vitamin C does not cause significant changes in the serum and
substances—surgery is currently the only method to remove urinary levels of oxalate. It is suggested that the results
calcium oxalate uroliths from the urinary tract. Small urocys- described previously may be explained as the effect of non-
toliths can be removed by voiding urohydropropulsion.15 In enzymatic conversion of ascorbate into oxalate during analy-
some patients, however, calcium oxalate uroliths are clinically sis.19 At present, a diet moderately restricted in protein, calci-
silent, obviating the need for surgical intervention. Complete um, oxalate, and sodium may be considered to prevent recur-
obstruction or progressive deterioration in renal function rence of calcium oxalate uroliths in dogs.14

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actively reabsorbed in the proximal tubules. Cystinuric dogs

BOX 2 reabsorb a much smaller proportion of the amino acid from
Recommendations for calcium oxalate the glomerular filtrate, and some may even have net cystine
urolith prevention excretion.20 The solubility of cystine in urine is pH dependent,
and it is relatively insoluble in acid urine but becomes more
1 Obtain baseline data (postsurgical radiography,
soluble in alkaline urine. The exact mechanism of cystine
complete urinalysis, serum concentration of calcium,
renal functioning tests) to evaluate effectiveness of urolith formation is unknown. Although increased urinary cys-
surgery, renal function and calcium homeostasis tine excretion is found in both males and females, uroliths are
2 If hypercalcemic, correct underlying cause most commonly found in males.
3 If normocalcemic, consider diets with reduced In a Swedish study, the urinary excretion of 20 amino acids
calcium, oxalate, sodium, and protein that do not was investigated in 24 stone-forming cystinuric dogs and 15
promote formation of acidic urine. Ideally, diets should normal dogs.21 Compared with the normal dogs, most cystin-
contain additional water and citrate and have adequate uric dogs showed significantly increased excretion of cystine,
phosphorus and magnesium
lysine, arginine, ornithine cystathionine, glutamic acid, threo-
4 Increase urine volume (add water to food, but avoid
excessive dietary sodium supplements) nine, and glutamine. A most significant finding was the great
5 Re-evaluate patient in 2–4 weeks to verify dietary variation in urinary cystine excretion. Seven of 24 cystinuric
compliance (urine specific gravity, pH, and sediment dogs showed normal cystine excretion at the time. This sug-
and serum creatinine) gests that factors other than excretion of cystine have to be
6 If calcium oxalate crystals and aciduria persist, considered as causes of the formation of cystine uroliths. In a
consider additional potassium citrate recent study, the clinical features and metabolic renal abnor-
7 Re-evaluate patient in 2–4 weeks to verify dietary
malities in 11 cystinuric Newfoundlands were described.20 In
compliance (urine specific gravity, pH, and sediment
and serum creatinine). If calcium oxalate crystals this study, however, all affected dogs persistently excreted
persist, consider vitamin B6 supplementation (2–4 excessive amounts of cystine compared with other related
mg/kg, q 24–48 hr) Newfoundlands without cystinuria. In the same study, the
8 After 3–6 months, re-evaluate patient to verify dietary mode of inheritance of cystinuria was evaluated.Although clin-
compliance, crystalluria, and urolith recurrence. If no ical signs of urinary obstruction were observed only in males,
uroliths are present, continue present therapy and re- cystinuric male and female offspring were produced from non-
evaluate in 3–6 months. If uroliths have recurred, cystinuric parents, consistent with an autosomal recessive
consider non-surgical removal. If unsuccessful, surgery
mode of inheritance. Obligate heterozygotes did not have clin-
can be considered if clinical signs attributable to
urocystolithiasis are present. If clinical signs are not ical signs and had normal urinary cystine content and renal
present, continue therapy to minimize urolith growth amino acid reabsorption.
Surprisingly, cystine uroliths are often not recognized until
maturity, with the average age of detection being approximate-
Thiazide diuretics ly 3 to 5 years. Because cystinuria is an inherited defect,
Although the use of thiazides in people has become common, uroliths commonly recur within 6 to 12 months (in some dogs,
the role of these substances in calcium oxalate urolith preven- within 4 to 8 weeks) unless prophylactic therapy is initiated.
tion is far from clear. The limited clinical experience in dogs Apart from the uroliths, cystinuric dogs have no other defects
makes this preventative measure unsafe. and normal renal function, and the disease would have
remained a physiological curiosity if cystine had not been the
Citrates least soluble naturally occurring amino acid, and thus poten-
Citrates form salts with calcium that are more soluble than tially leading to the formation of cystine uroliths.
calcium oxalate and are therefore calcium oxalate crystal
inhibitors. However, there have been no studies of the efficacy Characteristics, prevalence and diagnosis
of citrate in dogs with calcium oxalate urolithiasis. Cystine uroliths (Figure 4) account for 3.5% to 27% of the
canine uroliths, probably depending on the breed of dogs
CYSTINE UROLITHIASIS encountered in specific surveys. Many breeds of dogs have
Etiopathogenesis and biological behavior been reported to develop cystine uroliths. In Sweden and Ger-
Cystinuria is an inborn metabolic disease characterized by many, cystine urolithiasis is particularly a problem in the dachs-
excessive urinary excretion of cystine and the dibasic amino hund, and it accounts for approximately 4% and 18.8% , respec-
acids lysine, arginine, and ornithine. In normal dogs, circulating tively, of uroliths analyzed from the dog populations in those
cystine is freely filtered at the glomerulus, and most of it is countries.22 Although, cystinuria is found in both males and

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R1–S–S–R1 + R2– SH R1–SH + R2–S–S–R1

L-cystine 2-MPG Cysteine 2-MPG-cysteine

(less soluble) (soluble) (soluble) disulfide
(soluble)

Figure 5
Disulfide exchange reaction.

dietary sodium restriction.3 Our own preliminary studies indi-

cate that the effect of dietary sodium restriction in dogs might
be the same as for humans.

Figure 4 Increase of diuresis

Canine cystine uroliths. Increase of water intake provides a progressive reduction in
urinary cystine concentration and reduces the likelihood of
females, cystine uroliths have been reported most commonly precipitation.
in male dogs.22
The presence of flat hexagonal cystine crystals provides Alteration of solubility
strong support for a diagnosis of cystinuria. However, not all Cystine solubility can be enhanced by inducing an alkaline pH,
dogs with cystine uroliths have concomitant cystine crystal- but the solubility does not increase significantly until the pH is
luria. If a sufficient quantity of cystine is present in urine (>10 above 7.5.Administration of bicarbonate and citrate, for exam-
mmol/mol creatinine), the cyanide-nitroprusside test result for ple, has been advocated for improving solubility, but the
cystine will be positive.23 False-positive reactions due to med- author’s clinical experience, as well as that of others, suggests
ication with sulfur-containing drugs have been reported, but that not much practical benefit is achieved.23
the author’s experience is that this test is a reliable and simple
diagnostic procedure. For quantitative measurement of urinary Conversion to a more soluble compound
cystine excretion, 24 hour urine should be collected and quan- Chemical modification of the cystine molecule into a more sol-
tified by, for instance, ion exchange chromatography.21 uble form with D-penicillamine or 2-mercaptopropionylglycine
(2-MPG) has been suggested. This would be expected to
Treatment and prevention decrease cystine excretion into the urine and to diminish the
Current recommendations for dissolution and prevention of likelihood of urolith formation (Figure 5). Although D-penicil-
cystine uroliths encompass reducing the urine concentration lamine is effective in preventing the formation, and sometimes
of cystine and increasing the solubility of cystine in urine.Ther- the dissolution, of cystine uroliths, there are frequent compli-
apeutic approaches may be divided into four categories: cations that limit its use. In dogs, the most prominent side
effect is vomiting. Another property of penicillamine is chela-
■ reduction and change of dietary protein intake, aimed at tion of metals. In a study of 11 normal beagles given D-penicil-
reducing cystine production and excretion lamine orally and intravenously, significantly increased excre-
■ increase of diuresis tions of calcium, copper, zinc, chromium, cobalt, iron, and mag-
■ increase of cystine solubility nesium were found.24
■ conversion of cystine to a more soluble compound. 2-MPG is chemically related to D-penicillamine but has a high-
er oxidation-reduction potential and may therefore be more
Dietary modification effective in a disulfide exchange reaction.A clinical study was per-
Attempts have been made to design diets low in methionine to formed on 25 cystinuric dogs receiving oral treatment with 2-
decrease the excretion of cystine in humans, mostly with dis- MPG for periods of between 1 and 6 years.23 The drug was effec-
appointing results. At the Swedish University of Agricultural tive in urolith dissolution when given at a dose of approximately
Sciences, we have used a protein-restricted diet designed for 40 mg/kg.Thus, in 15 dogs with uroliths found in the bladder on
dissolution of canine struvite uroliths in two dogs with cystine 17 occasions, complete urolith dissolution was achieved on 9
uroliths; the uroliths did not dissolve.23 Studies in humans con- occasions (53%). For prophylactic therapy, a dose of 30 mg/kg is
clude that, despite a defective proximal tubular reabsorption of recommended. Most dogs tolerate 2-MPG well, although tran-
cystine in cystinuria, the reabsorption can be increased by sient side effects, such as thrombocytopenia, may occur.23

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With uroliths Without uroliths

2-MPG 2-MPG
40 mg/kg 30 mg/kg

Clinical examination every 4th week:

1. Urolith size, number (X-ray/ultrasound) Urolith recurrence No urolith recurrence
2. Blood (hemoglobin, thrombocytes,
creatinine, alkaline phosphatase)
3. Urine (protein, sediment, cyanide-
nitroprusside reaction, free cystine,
and 2-MPG-cysteine concentrations)

Urolith dissolution Surgery Individualized 2-MPG treatment

depending on periodic investigation of:-
1. Urinary free cystine and 2-MPG
cysteine disulfide concentration,
2-MPG
cyanide-nitroprusside reaction
30 mg/kg 2. Clinical signs of side effects

Figure 6
Algorithm for evaluation and handling of cystinuric dogs using 2-mercaptopropionylglycine (2-MPG). From Hoppe et al23

Figure 6 summarizes the author’s recommendations for the uricase to allantoin, which is excreted by the kidneys and is
evaluation and handling of cystinuric dogs with and without very soluble. In Dalmatians, only 30% to 40% of the uric acid is
uroliths. converted to allantoin. The defective uric acid metabolism in
Dalmatians is thought to be due to impaired transport of urate
URATE UROLITHIASIS across the hepatocyte cell membrane.Also, intestinal uptake of
Etiopathogenesis and prevalence hypoxanthine and urate is delayed and renal reabsorption of
Urate uroliths are relatively uncommon in dogs, comprising urate in the proximal tubules is reduced in Dalmatians. The
approximately 2% to 8% of uroliths analyzed.2,12 These uroliths definitive cause of urate urolith formation in this breed, how-
most commonly comprise ammonium acid urate (also known ever, remains unknown. As all Dalmatians excrete increased
as ammonium urate). Uroliths composed of sodium acid urate quantities of urate in their urine, and only a few form urate
and uric acid may occur but are uncommon. stones, this is a predisposing rather than a primary cause of
Various breeds of dogs have been reported to develop urate urolith formation.
urolithiasis. While this type of urolith is commonly encoun- Regardless of cause, severe hepatic dysfunction may predis-
tered in Dalmatians, approximately 30% to 60% are found in pose dogs to urate urolithiasis, especially ammonium urate
other breeds.12 In both Dalmatians and other breeds, the uroliths.A high incidence of ammonium urate uroliths has been
uroliths most frequently occur in males (70%) and are most observed in dogs with portal vascular anomalies. Hepatic dys-
frequently detected in dogs aged 3 to 6 years.25 Following sur- function in these dogs is associated with reduced hepatic con-
gical removal, the recurrence rate has been found to be as high version of uric acid to allantoin and ammonia to urea.
as 33% to 50% in all breeds.
In non-Dalmatian breeds, almost all the urate formed from Characteristics
degradation of purine nucleotides is metabolized by hepatic Urate uroliths (Figure 7) usually have a smooth surface. In the

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BOX 3
Recommendations for medical dissolution
of ammonium urate uroliths

1 Feed a calculolytic diet restricted in purine

2 Initiate therapy with allopurinol (30 mg/kg/day, divided
BID or TID)
3 If necessary, supplement the diet with potassium
citrate to achieve urine pH 7.0
4 If necessary, eradicate or control urinary tract
infection with appropriate antimicrobial agents
5 Assess the urinary tract by radiography or
ultrasonography every fourth week to determine
Figure 7 persistence of uroliths and progress of dissolution
Canine ammonium urate uroliths. 6 Evaluate serial urinalyses; pH, specific gravity, and
sediment for urate crystals
7 Continue the full dissolution protocol until 1 month
following confirmation of disappearance of uroliths by
Dalmatian they are most often located in the bladder, whereas
radiography or ultrasonography
in dogs with portal vascular anomalies, both kidneys are also
usually involved. Ammonium acid urate uroliths are poorly
radiopaque and can be difficult to detect on plain radiographs.
Ultrasonography is ideal for detection of radiolucent bladder BOX 4
uroliths.
Recommendations for ammonium urate
urolith prevention
Treatment and prevention
Potential risk factors for ammonium urolithiasis in dogs include 1 Feed a diet restricted in purine
increased renal excretion and urine concentration of uric acid; 2 If necessary, supplement the diet with potassium
increased renal excretion and urine concentration of ammo- citrate to achieve urine pH 7.0
nia; low urine pH; presence of promoters of ammonium urate 3 Evaluate the urine and the urinary tract by urinalysis
crystal formation; and absence of inhibitors of ammonium and radiography or ultrasonography every 1–2 months
urate crystal formation and aggregation. 4 Evaluate urine uric acid and/or xanthine concentration
Recommendations for medical dissolution of canine ammo- 5 If recurrence of uroliths, refer to recommendations
for dissolution of urate uroliths
nium acid urate uroliths (Boxes 3 and 4) include:
6 If no recurrence after 6 months, evaluate every 2–4
months
■ calculolytic diets
■ administration of xanthine oxidase inhibitors (allopurinol)
■ alkalinization of urine Xanthine oxidase inhibitors
■ eradication or control of urinary tract infections where nec- Allopurinol binds to and inhibits the action of xanthine oxidase
essary. (Figure 8), thereby decreasing the production of uric acid by
inhibiting the conversion of hypoxanthine to xanthine and of
Calculolytic diets xanthine to uric acid.Within a few days, this results in a reduc-
The aim of dietary modification is to reduce urine concentra- tion in the concentration of uric acid in serum and urine. The
tion of ammonium and urate. Studies have shown that a pro- recommended dose for dissolution of ammonium acid urate
tein-restricted diet, formulated to minimize uric acid excretion uroliths in dogs is 30 mg/kg/day, divided BID or TID. If urate
and supplemented with potassium citrate to promote urine crystalluria or hyperuricosuria persists after uroliths are dis-
alkalization, is associated not only with a reduction in urinary solved, allopurinol may be given at a dose of 10 to 20
excretion of uric acid and ammonia but also with alkalinuria mg/kg/day.To determine a safe and effective dosage of allopuri-
and polyuria, which may be beneficial in the management of nol in dogs, measurement of uric acid and/or xanthine con-
ammonium urate uroliths in dogs.26 It was also shown that this centration is important—allopurinol has been hypothesized to
diet was associated with dissolution of ammonium urate induce xanthine uroliths by impairing the enzymatic conversion
uroliths. of xanthine to uric acid.27

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 T h e L o w e r U r i n a r y Tr a c t

Before treatment
xanthine xanthine
oxidase oxidase uricase
Hypoxanthine Xanthine Uric acid Allantoin

After treatment
Allopurinol

xanthine xanthine
oxidase oxidase
uricase
Hypoxanthine Xanthine (Uric acid Allantoin)

Figure 8
Action of allopurinol as xanthine oxidase inhibitor.

Alkalinization uroliths in dogs. Definitive determination of chemical type. J Am Vet Med

Assoc 185, 983–988
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14 Osborne CA, Poffenbarger EM, Klausner JS, Johnston SD, Griffith DP
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16 Kok DJ, Iestra JA, Doorenbos CJ, Papapoulos SE (1990) The effect of
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