Struvite stones are significantly morecommon in female dogs than in male dogs.

The average age of dogs with struvite stonesaccording to one European study was 7.0 years8

(45) (USA: 5.9 years7) but struvite stones canalso occur in dogs less than 1 year old.

Struvite stones (magnesium ammonium phosphate hexahydrate) 57

Struvite stones(magnesium ammoniumphosphate hexahydrate)

INTRODUCTIONStruvite stones (magnesium ammoniumphosphate hexahydrate – MgNH4PO4·6H20)are mostly white to light yellow; the surface canbe microcrystalline and worn smooth. Manystones also have very well formed crystalstructures at the surface (42, 43). They presentas multiple stones or large single stonespredominantly in the bladder.

EPIDEMIOLOGYIn the past, struvite stones were the mostcommon form of stone in dogs. During the1990s, this trend changed, particularly in theUSA, in favour of calcium oxalate stones (Table17). Although the percentage of struvite stoneshas declined in other regions as well, this doesnot mean that the absolute incidence rate hasdecreased. Struvite stones appear to be morecommon in certain breeds (Table 18).

Since struvite stones in dogs are primarilylinked to urinary tract infections, it is possibleto assume a susceptibility to urinary tractinfections in predisposed breeds such as thePekingese, Cocker Spaniel, and Shih Tzu. Theshort urethra of female animals predisposesthem to urinary tract infections; an increased

incidence of struvite stones is therefore to beexpected in the bitch. This is confirmed in theoverall evaluation of the animals in Table 18where the female:male ratio = 1:0.75 (n =7,697); it is also seen in a European study, withboth entire and neutered dogs (female:maleratio = 1:0.49)(44).8

Struvite stones in dogs are primarily linked tourinary tract infections.

In Germany, struvite stones are predominantlyfound in female animals of certain breeds, e.g. thePekingese (female:male ratio = 1:0.4) and ShiTzu (female:male ratio = 1:0.4).10 A Canadianstudy also found that struvite stones have a higherprevalence in female dogs in the following breeds:Miniature Schnauzer, Shih Tzu, Bichon Frisé,Lhasa Apso, and Yorkshire Terrier.24 However,there are some breeds where the males have morestruvite stones than the females,e.g. BerneseMountain Dog (female:male ratio = 1:4.8),Cocker Spaniel (female:male ratio = 1:1.9) andGerman Shepherd Dog (female:male ratio = 1:3.0).10 Beside urinary tract infections, theobstruction of urinary flow due to gravel throughthe long urethra is a contributory factor in maledogs. The predominant occurrence of struvitestones in specific breeds is accounted for in somepublications by the formation of stones understerile conditions.9,134

CHAPTER 2 Urinary stones in dogs56

42 43

42 Struvite stone from a dog, mulberry-shapedstructure.

Table 17 Changes in the percentage of dogspresenting with struvite stones (1984–2003).

Percentage ofCountry Date struvite stones

USA 1984 70%318

1997 45%28

Germany 1990–1992 61%8

1999–2001 54%8

Canada 1998–2003 44%29

Czech Republic 1997–2002 39%23

Benelux 1994 5%24a

2003 40%24a

Table 18 Breeds of dog in whom struvite stonespredominate (total number of stones, n = 4,996).8

Share of struvite

Breed (total number of stones) stones (%)

Bernese Mountain Dog (n = 90) 96

Bull Terrier (n = 68) 91

Golden Retriever (n = 53) 91

Pekingese (n = 186) 85

Cocker Spaniel (n = 379) 85

German Shepherd (n = 111) 84

Shih Tzu (n = 194) 81

Crossbreed (n = 1,365) 68

West Highland White Terrier (n = 169) 62

Lhasa Apso (n = 57) 61

Poodle (n = 406) 60

Dachshund (n = 1,418) 60

43 Struvite crystal in urine sediment, scanningelectron microscopic image.

44

44 Gender distribution of dogs with struvitestones, European study 1999–2001 (totalnumber n = 4,082; struvite stones n = 1,991).8

4545Age distributionof dogs withstruvite stones in a European study 1999–2001 (n = 1,991).8

Unknown1.9% Male, entire

26.9%

Male,neutered

5.5%

Female46.2%

Female,neutered

19.5%

18

16

14

12

10

8

6

4

2

0

%

<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21>21Age (years)

energy thereby dramatically reducing theconcentration of citrate in the urine. Citrate is apowerful complexing agent for calcium andmagnesium ions and thereby a potent inhibitor ofcrystallization in urine even in the presence of aninfection. This means that other phosphatesbesides struvite, such as carbonate apatite, cancrystallize and serve as mixing partners in theformation of the stones. Infection-inducedstruvite stones can occur and grow very quickly(2–8 weeks after infection with urease-producingStaphylococcus spp.).135

Sterile struvite stones have been reportedwhere diets are high in minerals and producehigh ammonium concentrations and alkalineurine.134

Due to the higher incidence rate inindividual dog breeds, a genetic predispositionfor struvite stone formation has not been ruledout. For example, recurrent struvite stoneswere found in three related English CockerSpaniels with no urinary tract infection, butwith an alkaline urine pH.134

Newberyite (MgHPO4·3H2O) has rarelybeen diagnosed in dogs with urinary stones. Asyet, nothing is known about the exactpathogenesis of this type of stone, but thissubstance can crystallize in weakly acidic urineat high magnesium concentrations, so a sterilepathogenesis must be assumed.

The prolonged storage of struvite stones(MgNH4PO4·6H2O) and exposure to warmtemperatures can split the water in the crystalsleading to the artificial occurrence of dittmarite(MgNH4PO4·1H2O).136 Dittmarite is not atrue urinary stone but can be seen during theanalysis of old stones.

DIAGNOSISUrinalysis• Smell: possibly of ammonia in urinary tract

infections.• Specific gravity: mostly >1.030 (aim:

<1.015).• pH: in urinary tract infections in fasted

dogs >7.0.

Struvite stones (magnesium ammonium phosphate hexahydrate) 59

The majority of struvite stones in dogs occurin the bladder. In male animals, small stones aremore common in the urethra; therefore, boththe bladder and the urethra can be affected.Struvite stones are rarely found in the upperurinary tract (kidneys, ureters) (Table 19).

PATHOGENESISCalcium and magnesium phosphate do notdissolve readily in alkaline urine. Themonobasic dihydrogen phosphate anion(H2PO4

-) is present in acidic urine, and formsvery soluble salts. As the pH increases,monohydrogen phosphate anions (HPO4

2-)create less soluble calcium salts in weakly acidicurine. However, sufficient free phosphate ions(PO4

3-) are only available at alkaline pH values,allowing the occurrence of struvite stones. Theconditions required for the formation ofstruvite crystals include sufficient magnesium,ammonium, and phosphate concentrations inthe urine, but the decisive factor is an alkalineurine pH (46).

CHAPTER 2 Urinary stones in dogs58

The supersaturation of urine with magnesiumammonium phosphate hexahydrate in dogs isgenerally caused by urinary tract infections withurease-producing bacteria (see Table 8, p. 21; 47).Staphylococcus spp. have been most commonlyfound in dogs, whereas in humans Proteus spp. arethe predominant agents of urease production.Urea is split by urease (see 11), causing the urinepH to increase to >7.0. Furthermore, thesebacteria metabolize citrate for the production of

Table 19 Location of struvite stones in dogs,European study 1999–2001 (n = 1202).8

Location %

Kidney/ureter 0.7

Bladder 72.2

Bladder/urethra 21

Urethra 6.1

46

46 Diagrammatic presentation of the occurrence of struvite crystals in urine.

Struvite crystal6x

H2O

AlkalinepH

PO43–

H+

HPO42–

NeutralpH

H+

H2PO4–

H+

H3PO4 AcidicpH

(Magnesium)

NH4+

H+

NH3

(NH4+) (Mg2+) (PO4

3–)

47

47 Diagram of the pathogenesis of infection-induced struvite stones in dogs.

Infection-induced calculi in dogs

SupersaturationCrystalluria

URINARY STONEStruvite

MgNH4PO4.6H2O

Carbonate apatiteCa10(PO4,CO3)6(OH,CO3)2

Urea splitting Breed Gender

female > maleDiet Fluid intake↓

NH4+↑ pH↑ Citrate↓ Ca↑ Mg↑ P↑ Specific gravity↑

bladder, or are passed spontaneously, a stoneanalysis should always be requested. Furthertherapeutic procedures can then beimplemented, as experimental and clinicalstudies have shown that struvite stones can bedissolved in vivo.137-140 Prophylaxis is onlypossible if the composition of the stone isknown.

Struvite can appear as a mixing partner in alltypes of urinary stone. As with any case ofurolithiasis, a secondary infection may bepresent. Particular attention should be paid tothe accompanying infection in this case, as it isconsidered to be the primary cause of theurolithiasis.

Test kits for chemical urinary stone analysisare very inaccurate and thereforeobsolete.3,100,141

Analysis using infrared spectrometryproduces reliable qualitative and quantitativeresults. See Chapter 1, p. 30.

TREATMENT AND LONG-TERMPREVENTIONTreatmentThe following measures should be taken in thetreatment of dogs with struvite stones in thekidneys or bladder:• Specific treatment of the urinary tract

infection.• Removal of obstruction if present.• Abundant fluid therapy to dilute the

organisms and reduce the relativesupersaturation, in particular the specificgravity of the urine should be brought to<1.015.

• Removal or dissolution of urinary stones.• Regular monitoring to allow rapid

detection of recurrence.

Struvite stones in the ureter or urethra cannotbe dissolved as too little urine passes through toproduce a conducive environment for this.Other measures must be used in these cases(surgery, urohydropropulsion, endoscopy,lithotripsy). See Chapter 1, pp. 49–52.

Treatment of urinary tract infectionsIn acute cases treatment of the urinary tractinfection can be initiated prior to the results ofantibiotic sensitivity testing with a β-lactamantibiotic (ampicillin, amoxicillin–clavulanicacid, cefovecin), a fluoroquinolone

(enrofloxacin, marbofloxacin), or trimethoprimsulphonamide. Ideally, culture and sensitivitytesting should be performed prior to initiationof treatment, so that the appropriate treatmentcan subsequently be introduced. A sensitivitytest is essential if urinalysis reveals continuedinfection at the follow-up check and if struvitestones do not decrease in size despite the use ofa specific diet and the administration ofantibiotics.

The most common bacteria found in dogswith urolithiasis include Staphylococcus, Proteus,Escherichia coli, Streptococcus, Klebsiella,Pseudomonas and Enterobacter species.142,143 Incases of struvite stones, only one species isusually isolated, the most common being theurease-forming Staphylococcus spp.123

Dietary urinary acidification is not sufficientto dissolve the stones in the presence of urease-producing bacteria. The urine must thereforebe kept sterile until undersaturation with stone-forming crystals is achieved. Often viablebacteria can be found within the struvite stonesthemselves, and these can re-colonize thebladder during stone dissolution. Consequentlyantibiotic therapy at the full dose should becontinued throughout the stone dissolutionphase (verified on radiographs orultrasonography) and then continued for afurther 4 weeks after dissolution. However, ifthe urine is initially sterile the administration ofantibiotics can be foregone. If additionaldiuresis is induced, the antibiotic dose shouldbe adapted to maintain the minimuminhibitory concentration in the diluted urine.Using too low an antibiotic dose or a too shortcourse of antibiotics can lead to the recurrenceor renewed growth of bacteria once dissolutionhas commenced.

The dissolution of struvite stones withantibiotics alone and without a dietary changeis rarely possible66 and is not recommended.Dissolution will take significantly longer (manymonths) than with a combination of antibiosisand dietary change (several weeks).

The full dose of antibiotics must beadministered throughout the period in

which the struvite stones are dissolved andfor 4 weeks thereafter.

Struvite stones (magnesium ammonium phosphate hexahydrate) 61

• Nitrite on dipsticks: not reliable in dogs.• Bacterial investigation on dipsticks is not

reliable in dogs.• Urine sediment: characteristic coffin-lid-

shaped crystals (29a & b) (not definiteproof of struvite stones!).

In cases of urolithiasis, the urine should becollected under sterile conditions andsubmitted for culture and antibiotic sensitivitytesting. The colony count in the urine sampledepends heavily on the withdrawal technique(see Table 12, p. 42), urine should be thereforebe withdrawn wherever possible usingcystocentesis. In dogs with urinary tractinfections a single bacterial species is usuallypresent (multiple species often suggestcontamination).

Computer programs (EQUIL,SUPERSAT92;94) can be used to calculate therisk of occurrence of struvite stones followingthe quantitative urinalysis.

Blood testsSigns of inflammation in the blood such asleucocytosis with neutrophilia and a left shift,hyperglobulinaemia or increased acute phase

proteins (C-reactive protein, increasederythrocyte sedimentation rate) are usually onlyfound in urinary tract infections due topyelonephritis. A urinary tract infection of thelower urinary tract, in particular the bladder,does not produce any inflammatory changes inthe blood.

Struvite stones only cause serumbiochemistry changes if they are in the kidneysand cause subsequent renal failure. Usually thebiochemistry is unremarkable.

Diagnostic imagingStruvite stones are radiopaque and can beclearly seen on survey radiographs (see Table 13,p. 45). It is important to image the entireurinary tract and the complete length of theurethra. Struvite stones are round with asmooth surface, often multiple but sometimessolitary and very large (48). As with all urinarystones, an ultrasound scan shows a clearhyperechoic area with acoustic shadows thatmove when the animal changes position.

Urinary stone analysisIf sediment, stone fragments or small stones areflushed out from the urinary tract or the

CHAPTER 2 Urinary stones in dogs60

48

48 Radiograph of a 9-year-old neutered female Pekingese with multiple bladder stones of varyingsizes and with smooth surfaces. The stones (100% struvite) were removed surgically, as the dog hadproblems passing urine.

which in turn leads to the production of lessconcentrated urine thereby promoting diuresis.

A stone-dissolving diet should only beadministered where there is a clear indication,and in the absence of concurrent diseases such ascardiac failure, hypertension, or nephroticsyndrome. In pregnant, lactating, and growinganimals, these diets should only be used as short-term measures. A diet with too low a proteincontent can impair postoperative wound healing.High-fat diets should not be given to animalswith altered fat metabolism or with pre-existingpancreatitis, or to Miniature Schnauzers withfamilial hyperchylomicro naemia.

Stone-dissolving diets should be given untilthe stones have completely disappeared and for 4weeks afterwards, so that any very small stonesthat are no longer visible on radiogaphs orultrasonography, are eradicated. If not eradicated,these could be a nidus for new stones.

It takes an average 3 months (2 weeks to 7months) to completely dissolve struvite stoneslinked to urinary tract infections using dietarymeasures combined with appropriate antibiotic

treatment.66,145 Sterile struvite stones can bedissolved more quickly (average of 6 weeks; 1–3months).146 Dietary stone dissolution should bechecked initially after 4 weeks and only becontinued if an improvement is seen. Follow-upconsultations should then be performed every 4weeks and should include a history, clinicalexamination, radiographs, blood tests (urea,albumin, phosphorus), and urinalysis (specificgravity, dipstick, sediment examination, culture,and sensitivity). The serum of dogs on a struvitedissolution diet has reduced levels of urea,phosphorus, and albumin (Table 20).145

Although nutritional studies have shown that thisdoes not present any clinical problems in healthydogs, such changes demonstrate the unsuitabilityof such diets in the long term. Reduced urealevels are a good indication of owner compliance.

A struvite dissolution diet should not be usedprophylactically or as a long-term

maintenance diet. In puppies and pregnantbitches, it should only be used in cases with a

strong indication, and for a maximum ofseveral weeks.

Struvite stones (magnesium ammonium phosphate hexahydrate) 63

Removal of an obstructionThe removal of struvite stones from the lowerurinary tract with surgery or urohydro -propulsion (see Chapter 1) is only necessary ifthey are causing an obstruction (49) or if thereis a high risk of obstruction and insufficientopportunity to monitor the dog. The surgicalremoval of struvite stones is further indicated ifthe bladder lumen is filled with many and/orvery large stones, if obstructing urethral stoneswere flushed into the bladder or if the assumedcomposition of the stone suggests thatdissolution is not possible. Surgical removal ofstruvite stones from the kidneys (renal calculus)should be weighed against the risk of possiblecomplications (such as intraoperative damage tokidney tissue); however, medical or dietarysolutions are not straightforward as the stonescannot be sufficiently exposed to acidic,antibiotic-containing urine. The surgical removalof stones also provides the opportunity ofcorrecting anatomical defects in the urinary tract.

The disadvantages of surgery include thoseassociated with the anaesthesia, hospitalization,

aftercare, and so on. There is also a risk ofstricture formation with repeated surgical stoneremoval from the ureters or urethra. It has beenshown that struvite stones recur more quicklyafter surgery than after administration ofdietary dissolution.66 This can probably beaccounted for by the fact that not all stones areremoved intraoperatively and small stones formthe nidus for the formation of new stones.144

Dietary measuresA change of diet can be effective on its own forthe dissolution of struvite stones. Struvite stonedissolution diets have a relatively low content ofhigh-value protein (15–20%), reduced calcium,magnesium, and phosphorus, and aresupplemented with sodium chloride topromote fluid intake.71 The moderate amountsof protein reduce the production of urea in theliver and thereby the amount of urea in thekidney interstitium and in the urine. There istherefore less urea for bacterial urease. Thereduced serum urea in the renal medulla alsoleads to a reduced concentration gradient,

CHAPTER 2 Urinary stones in dogs62

49

49 Multiple, small stones in the bladder and a somewhat larger stone in the detrusor area of a 6-year-old Dachshund. Due to the presentation of typical coffin-lid-shaped crystals and the urine pH (7.5)together with a urinary tract infection, struvite stones were assumed. The stones were removedsurgically as the obstruction made chemolysis impossible. The diagnosis was confirmed followingstone analysis (100% struvite).

Table 20 Comparison of the findings in history, clinical examination, blood tests, and urinalysis before, during,and after struvite stone dissolution.66

After successful Finding Before treatment During treatment treatment

Haematuria - to +++ - after a few days -

Abnormal urine odour - to +++ - after a few days -

Pollakiuria + to +++ rarely ↑ later ↓ -

Polyuria - to + + to +++ -

Small urinary stones spontaneously flushed out Possible Often (in female dogs) -

Serum urea >3.5 mmol/l 0.8–3.5 mmol/l According to diet

Serum albumin Normal ↓ by 5–10 g/l Normal

Serum phosphorus Normal Slight reduction Normal

Urine specific gravity Variable ±1.004 to ±1.015 Normal

Urine pH ≥7.0 Reduced (acid) Variable

Urine protein + to +++ Reduced to - -

Struvite crystals - to +++ Mostly - Variable

Other crystals Variable Variable Variable

Bacteria in the urine - to +++ Reduced to - -

Urine culture - to +++ Reduced to - -

urinary stone inside the body (pseudo -morphism, see 15). The occurrence ofweddellite stones is most commonly associatedwith hypercalciuria.

Calcium oxalate monohydrate (whewellite) ismonoclinic and the crystals present a variety ofshapes in urine sediment – dumbbell, ellipsoid,or long oval shaped (53). Whewellite stones aremicrocrystalline, very compact, hard andbrown to black in colour. The surface is mostlysmooth to rough and commonly has mulberry-shaped protrusions (51). It has been shownthat the occurrence of whewellite stones isoften linked to hyperoxaluria.149,150 Only

whewellite stones are found in primaryhyperoxaluria and they may also be seen withexcessive urinary oxalate excretion. In a studyof the analysis of urinary stones in dogs inEurope, pure weddellite stones (20%) weremore common than pure whewellite stones(5%).8 Weddellite stones grow quicker thanwhewellite stones and recurrence is morecommon. Contrary to the findings in Europe,more whewellite (44.7%) than weddellite(6.8%) stones were found in dogs in the USA.7

Mixed calcium oxalate stones usually containcarbonate apatite, as well as the two calciumoxalates.

Calcium oxalate stones 65

Commercial diets that change the urinecomposition markedly and help in struvitestone dissolution have been developed.

Medical measuresIn some countries, acetohydroxamic acid(12.5 mg/kg q12h orally)147 is licensed for useas an inhibitor of microbial urease in dogs forwhom an acid-inducing diet has provedunsuccessful. Acetohydroxamic acid reducesthe ammonia content of urine and inducesalkalinization, but does not have a significantantibiotic effect. Side-effects include anorexia,vomiting, haemolytic anaemia, and alteredbilirubin metabolism.

Amino acid preparations are an effectivesolution for sterile struvite stones, as theyprobably lead to acidification of the urine.148

There are no reports for infection-inducedstruvite stones.

The medical acidification of urine (e.g. withL-methionine) is not indicated in infection-induced struvite stones, since appropriateantibiotic administration and a special diet aresufficient. In sterile stones this can rarely beused to decrease the pH value to 5.8–6.2.

Difficulties encountered with dissolving stonesAs a general rule, large struvite stones takelonger to dissolve than smaller ones. Otherfactors that influence the speed of dissolution ofstruvite stones include: the number of stones,the location of the stones, and the presence ofother components in the stones such as calciumphosphate or calcium oxalate.

The following points should be checked ifstruvite stones cannot be dissolved: • Are they really pure struvite stones? • While the shell of the stone may be

struvite, the centre of the stone is notalways identical, so after the first successfulsigns of dissolution, the core does notbecome smaller.

• A lack of owner or patient compliance withfeeding (check blood urea).

• Inadequate antibiotic dose or not given forlong enough.

• Antibiotic resistance (urine bacteriologyincluding sensitivity test).

Prevention of recurrenceSuccessful prevention of recurrence is onlypossible if all stones have been dissolved and theinfection resolved. After stone dissolution,urinary tract infections should therefore beexcluded and the urine monitored every 2–3months in the first year. General prophylacticmeasures include: • Clean freely available drinking water.• Use of wet food, or special prophylactic

dry food.• Check the specific gravity of the urine, aim

for <1.020.• Possible increase in water intake.• Possible increase in sodium chloride for

further diuresis.• Check the urine pH, aim for 6.2–6.5.

Commercial foods are being developed whichwill influence the composition of urine for thelong-term prevention of struvite stones.

In mixed stones, a genetic anomaly such ascystine, urate or xanthine excretion may be thepredisposing factor for stone occurrence.

It is rarely necessary to administer long-termantibiotic treatment in dogs with persistenturinary tract infections. Predisposing factors forurinary tract infections should also be treated(diabetes, hyperadrenocorticism, urachaldiverticula).

Calcium oxalate stones

INTRODUCTIONCalcium oxalate urinary stones can occur in twodifferent mineralogical phases (50, 51), whichcan only be differentiated by the water contentof the crystal. Calcium oxalate dihydrate(weddellite) is tetragonal and produces typicalenvelope-shaped crystals in urine sediment (52,see also 29). Weddellite stones are primarilycomposed of well formed, hard, individualcrystals with an irregular surface. In urinesediment, weddellite crystals are almostcolourless and the stones they form are yellowto brown. Weddellite is unstable as a purechemical compound and restores itself tocalcium oxalate monohydrate (whewellite)when a molecule of water of crystallization isremoved. This means that weddellite can bestabilized in urine containing substances suchas magnesium and calcium.149 The conversionfrom weddellite into whewellite can occur in a

CHAPTER 2 Urinary stones in dogs64

51

51Whewellite – spherical urinary stones in adog.

50

50Weddellite – urinary stone in a dog with welldeveloped, sharp-edged crystals on the surface.

52

52Weddellite – twin crystal in urine sediment,scanning electron microscopic image.

53

53Whewellite – long oval crystal in urinesediment with adherent bacteria, scanningelectron microscopic image.