Chapter 40 · Chapter 40 Canine Calcium Oxalate Urolithiasis: Changing Paradigms in Detection,...

OVERVIEW

Uroliths composed of calcium oxalate monohydrate and calci-um oxalate dihydrate form as a result of the interaction of sev-eral different environmental and demographic risk factors, andseveral different metabolic disturbances.That is, not all calciumoxalate uroliths are “created in the same way.” Some of thesefactors are primary and some are compensatory. Identificationof primary and secondary abnormalities associated with calci-um oxalate urolithiasis is essential if therapy is to be consistent-ly safe and effective.

Of the biogenic uroliths that affect dogs, cats and people,those composed of calcium oxalate have been the most prob-lematic. However, substantial progress has been made in the last10 years. We predict that within the next 10 years, we willunderstand how to identify and safely modify the underlyingmechanisms involved with calcium oxalate urolithiasis. That is,within the next decade we will have reached our goal of makingthe surgical removal of uroliths a treatment of historical interest.

Calcium oxalate accounted for 38% of all canine uroliths sub-mitted to the Minnesota Urolith Center from 1981 to 2007(Table 38-8) and 41% (16,761 of 40,612) of all canine urolithssubmitted in 2007 (Figure 40-1) (Osborne and Lulich, 2007).Calcium oxalate also accounted for 43% of all upper urinarytract uroliths analyzed at our Center from 1981 to 2006 (Table38-9). From 2000 to 2006 calcium oxalate composed only 1%of uroliths retrieved from dogs less than 12 months old. Themean age of dogs at the time of calcium oxalate urolith retrievalwas approximately 8.5 years (range = one to 25 years; median =8.7 years). Males (74%) were affected more often than females(22%); the age of approximately 4% of affected dogs was notspecified. A total of 214 different breeds were affected includ-ing miniature schnauzers (18%), mixed breeds (14%), Yorkshireterriers (9%), Bichon Frises (8%), Shih Tzus (7%), Lhasa apsos(5%), Pomeranians (4%), dachshunds (3%), Maltese (3%),

Chapter

40Canine Calcium Oxalate

Urolithiasis: ChangingParadigms in Detection,

Management and PreventionJody P. Lulich

Carl A. Osborne

Lori A. Koehler

“A well-defined problem is half solved.”Carl A. Osborne

PREVALENCE AND MINERAL COMPOSITION

miniature poodles (3%), Chihuahuas (2%) and Jack Russell ter-riers (2%). Calcium oxalate uroliths were more commonlyremoved from the lower urinary tract (97%) than the upper uri-nary tract (3%).

Although different combinations of calcium oxalate saltshave been identified in canine uroliths, the predominant formencountered has been calcium oxalate monohydrate(whewellite; Table 38-8). Pure calcium oxalate monohydratehas been observed in dogs more frequently than pure calciumoxalate dihydrate (weddelite). A similar observation has beenmade in cats and people with calcium oxalate uroliths. Whencalcium oxalate salts occur in combination in human, feline andcanine uroliths, the dihydrate salt is usually found surroundinga nucleus of the monohydrate salt (Koide et al, 1982). The sig-nificance of this observation has not yet been confirmed,although it has been suggested that calcium oxalate dihydratemay form initially and then be converted to calcium oxalatemonohydrate (Leusmann et al, 1984; Otnes, 1983; Schubertand Brien, 1981; Tomazic and Nancollas, 1982). In people,detection of calcium oxalate dihydrate on the outside of aurolith may indicate recent formation, whereas detection ofexternal layers of calcium oxalate monohydrate indicates lack ofrecent urolith formation (Berenyl et al, 1972). If valid in dogs,this hypothesis would be of clinical significance because itwould help to determine if the disorders underlying calciumoxalate urolithiasis were persistent. This in turn would provideevidence of the need for continuous therapy to minimizeurolith recurrence. In one study, human patients with calciumoxalate dihydrate uroliths had more recurrences of uroliths thandid patients with calcium oxalate monohydrate uroliths(Leusmann et al, 1984).

Calcium oxalate monohydrate and dihydrate uroliths are typ-

ically dense and brittle; they have relatively small quantities(~3%) of matrix. Pure calcium oxalate monohydrate and calci-um oxalate dihydrate have different colors and shapes (Table40-1). In people, uroliths composed of calcium oxalate mono-hydrate frequently assume the shape of mulberries or jackstones(Otnes, 1983). To date, only a few canine calcium oxalate jack-stones have been observed at the Minnesota Urolith Center.

ETIOPATHOGENESIS AND RISK FACTORS

In order for calcium oxalate uroliths to form, urine must besupersaturated with calcium and oxalic acid.Therefore, increas-ing the urine concentration of calcium and/or oxalic acid pro-motes calcium oxalate crystal formation. Hypercalciuria hasbeen documented to occur in dogs with calcium oxalate uroliths(Lulich et al, 1991).

At one time it was thought that increases in urine oxalic acidconcentration promoted calcium oxalate urolith formation inpeople to a greater degree than comparable increases in urinecalcium concentration (Smith, 1991). Results of more recentstudies, however, indicate that oxalic acid and calcium con-tribute equally to urine supersaturation with calcium oxalate(Pak et al, 2004). Although hyperoxaluria apparently has notbeen documented to occur in dogs with calcium oxalateuroliths, the relationship between the concentrations of calciumand oxalic acid within the digestive and urinary tracts is funda-mental to understanding calcium oxalate urolithiasis.

Dietary Risk FactorsDietary ingredients that promote hypercalciuria or hyperox-aluria represent nutritional risk factors for calcium oxalate

Small Animal Clinical Nutrition856

Figure 40-1. Bar graph illustrating increased occurrence of canine calcium oxalate uroliths submitted to the Minnesota Urolith Center from1981 to 2007. Note the overall decline in struvite urolith submissions and the increase in calcium oxalate submissions. Key: MAP = magnesiumammonium phosphate (struvite), CaOx = calcium oxalate, CaP = calcium phosphate.

urolith formation (Tables 40-2 and 40-3).Therefore, reductionof dietary calcium and oxalate appears to be a logical therapeu-tic goal. However, it is not necessarily harmless. Reducing con-sumption of only one of these substances (calcium) mayincrease the availability of the other (oxalic acid) for intestinalabsorption and subsequent urinary excretion. To minimize thisundesirable shift in the modulation of oxalic acid absorptionfrom the intestine, reduction in dietary calcium should beaccompanied by an appropriate reduction in dietary oxalic acid.

Dogs with calcium oxalate urolithiasis frequently consumehuman food. Calcium oxalate is the most common urolith typerecognized in people living in developed countries. As peoplefeed their dogs the same dietary proportions and ingredientsthey feed themselves, it is logical to postulate that dogs wouldbe exposed to similar nutritional risk factors for urolith forma-tion (Table 40-2). Results of epidemiologic studies performedat the Minnesota Urolith Center support this hypothesis.

In addition to human food consumption, an associationbetween calcium oxalate urolithiasis and consumption of com-mercially available treats has also been recognized. The highsodium content of some commercial dog treats may helpexplain this association because sodium consumption promoteshypercalciuria (Lulich et al, 1992).

Certain dietary excesses and deficiencies have also been rec-ognized as potential risk factors. Excessive administration ofvitamin D, sodium or magnesium promotes hypercalciuria.Because ascorbic acid is a precursor of oxalate, excessive quan-tities of vitamin C should be avoided. Although dogs with cal-cium oxalate uroliths have not been evaluated for pyridoxinedeficiency, kittens fed pyridoxine-deficient foods exhibitedhyperoxaluria (Bai et al, 1989).

Other Risk FactorsCalcium oxalate uroliths have been recognized in many breedsof dogs (see Prevalence and Mineral Composition above).Infrequently encountered breeds include boxers, bloodhounds,coonhounds, Dalmatians, English bulldogs, Newfoundlands,German shorthaired pointers, Skye terriers, wirehaired terriers,golden retrievers, Labrador retrievers and St. Bernards.Approximately 74% of calcium oxalate uroliths have affectedmale dogs. Most were detected in adults (mean and median agewas eight to nine years).

Geographic location has been identified as a risk factor forcalcium oxalate urolith formation in people living in the UnitedStates (Mandel and Mandel, 1989). In a study of approximate-ly one million people, investigators observed a north-south andwest-east gradient such that people living in the southeasternU.S. (Alabama, Arkansas, Florida, Georgia, Louisiana, Mis-sissippi, North and South Carolina, Tennessee and Virginia)had the highest rate of urolith formation (Soucie et al, 1996).Studies evaluating geographic location as a risk factor for calci-um oxalate urolith formation in dogs have apparently not yetbeen reported.

Certain clinical conditions also represent potential risk fac-tors for calcium oxalate urolith formation. Hyperparathy-roidism, hyperadrenocorticism, hypervitaminosis D, paraneo-

plastic hypercalcemia and furosemide administration promotehypercalciuria. In people, intestinal resection, hereditary hyper-oxaluria and excessive ascorbic acid administration promotehyperoxaluria (Park and Pearle, 2007).

HypercalciuriaHypercalciuria can be localized into at least three subtypesaccording to the primary site of the underlying cause (i.e.,intestine, kidney or skeleton): 1) absorptive hypercalciuria ischaracterized by intestinal hyperabsorption of calcium, 2) renalhypercalciuria is characterized by impaired renal tubular reab-sorption of calcium and 3) resorptive hypercalciuria is charac-terized by bone demineralization.

Available evidence indicates that calcium homeostasis isprincipally achieved through the actions of parathyroid hor-mone (PTH) and 1,25-dicholecalciferol (1,25-vitamin D) onthe intestines, kidneys and skeleton. For example, states of low

857Canine Calcium Oxalate Urolithiasis

Table 40-1. Common characteristics of canine calcium oxalate uroliths.

Chemical Crystal names Formulas namesCalcium oxalate monohydrate CaC2O4•H2O WhewelliteCalcium oxalate dihydrate CaC2O4•2H2O WeddelliteVariations in mineral compositionCalcium oxalate monohydrate onlyCalcium oxalate dihydrate onlyCombinations of calcium oxalate monohydrate and dihydrateCalcium oxalate (monohydrate and/or dihydrate) mixed with

variable quantities of calcium phosphate. Variable quantities of struvite or ammonium acid urate may also be present.

Calcium oxalate (monohydrate and/or dihydrate) nucleus surrounded by other minerals especially infection-induced struvite

Physical characteristicsColor: Calcium oxalate monohydrate uroliths are usually tan orbrown. Calcium oxalate dihydrate uroliths are usually white orcream colored. Surfaces may be red to black if uroliths arecoated with blood.Shape: Variable. Calcium oxalate monohydrate uroliths are usu-ally round or elliptical and have a smooth, polished surface.Occasionally, they may develop a jackstone or mulberry shape.Calcium oxalate dihydrate uroliths and mixed calcium oxalatemonohydrate/calcium oxalate dihydrate uroliths are usuallyround to ovoid and have an irregular surface caused by protru-sion of sharp-edged crystals. Occasionally, they may develop ajackstone shape.Nuclei: Radial striations and concentric laminations may occur.Density: Very dense and brittle. Survey radiographs reveal thatcalcium-containing uroliths are radiodense compared with softtissue.Number: Single or multipleLocation: May be located in renal pelves, ureters, urinary blad-der (most common) and/or urethra.Size: Sub-visual to several centimetersPrevalenceApproximately 41% of all canine uroliths. More than 43% of

canine upper tract uroliths.May be recurrent (more than 50% recur by three years after

removal)Characteristics of affected canine patientsMore common in males (73%) than females (22%)Mean age at diagnosis is about eight years (range <1 to >25

years)Most commonly observed in miniature schnauzers, Lhasa

apsos, Yorkshire terriers, Shih Tzus and Bichon Frises

serum ionized calcium concentration result in compensatoryPTH- and 1,25-vitamin D-mediated mobilization of calciumfrom the skeleton, absorption of calcium from the intestine andconservation of calcium by the kidneys. High serum ionizedcalcium concentrations suppress release of PTH and produc-tion of 1,25-vitamin D. The result is decreased skeletal mobi-lization and intestinal absorption of calcium and enhancedrenal calcium excretion. Thus, it is apparent that hypercalciuriacan result from increased renal clearance of calcium due to: 1)excessive intestinal absorption of calcium, 2) impaired renalconservation of calcium and/or 3) excessive skeletal mobiliza-

tion of calcium. Although hypercalciuria can be localized ac-cording to the site of the apparent primary defect in calciumtransport, compensatory changes typically occur that involveother sites. For example, renal-leak hypercalciuria is associatedwith secondary hyperparathyroidism, which in turn is associat-ed with varying degrees of bone resorption of calcium andphosphorus and varying degrees of intestinal calcium absorp-tion. Absorptive hypercalciuria results in a positive calcium bal-ance, which in turn suppresses production and release of PTH,decreasing renal tubular reabsorption of calcium.

Hypercalcemic hypercalciuria results from increased glo-


Table 40-2. Some potential risk factors for canine calcium oxalate uroliths.

Diet Urine Metabolic status DrugsAcidifying potential Hypercalciuria Chronic metabolic acidosis Urine acidifiersHigh protein content Hyperoxaluria Males FurosemideHigh sodium content Hypocitraturia? Breed GlucocorticoidsExcessive calcium content Hypomagnesuria? Miniature schnauzers Sodium chlorideExcessive restriction of calcium Hyperuricuria? Miniature poodles Vitamin DLow moisture content Increased crystal promoters Lhasa apsos Ascorbic acidExcessive phosphorus restriction Decreased crystal inhibitors Yorkshire terriersExcessive magnesium content Urine concentration Shih TzusExcessive magnesium restriction Urine retention Bichon FrisesExcessive vitamin D content Older ageExcessive vitamin C content HypercalcemiaDeficient pyridoxine? Glucocorticoid excessHigh oxalate content Hypophosphatemia

Hyperoxalemia?Osteolysis?

Food itemsMeats

Bologna (M)Herring (M)Oysters (M)Salmon (H)Sardines (H)

VegetablesBaked beans (M)Broccoli (H)Collards (H)Lima beans (M)Spinach (M)Tofu (soybean curd) (M)

Milk and dairy productsCheese (H)Ice cream (H)Milk (H)Yogurt (H)

Breads, grains, nutsBrazil nuts (M)

MiscellaneousCocoa (M)Hot chocolate (M)

Table 40-3. Selected human foods to limit or avoid feeding to dogs with calcium oxalate uroliths.*

Key: M = moderate; feed in limited amounts. H = high; avoid feeding.*Adapted from Wainer L, Resnick VA, Resnick MI. Nutritional aspects of stone disease. In: Pak CYC, ed. Renal Stone Disease,Pathogenesis, Prevention, and Treatment. Boston, MA: Martinus Nihoff Publishing, 1987; 85-120. Burroughs M. Renal diseases anddisorders. In: Nelson JK, Moxness KE, Jensen MD, et al, eds. Mayo Clinic Diet Manual, 7th ed. St. Louis, MO: Mosby, 1994; 208-209.

Moderate/high-calcium foods Moderate/high-oxalate foods

Food itemsMeats

Sardines (M)Vegetables

Asparagus (M)Broccoli (M)Carrots (M)Celery (H)Corn (M)Cucumber (H)Eggplant (H)Green beans (H)Green peppers (H)Lettuce (M)Spinach (H)Summer squash (H)Sweet potatoes (H)Tofu (H)Tomatoes (M)

FruitsApples (H)Apricots (H)Cherries (M)Most berries (H)

Oranges (M)Peaches (M)Pears (M)Peel of lemon, lime or orange (H)Pineapple (M)Tangerine (H)

Breads, grains, nutsCornbread (M)Fruitcake (H)Grits (H)Peanuts (H)Pecans (H)Soybeans (H)Wheat germ (H)

MiscellaneousBeer (H)Chocolate (H)Cocoa (H)Coffee (M)Tea (H)Tomato soup (H)Vegetable soup (H)

merular filtration of mobilized calcium, which overwhelmsnormal renal tubular reabsorptive mechanisms. This phenome-non is called resorptive hypercalciuria because excessive boneresorption is associated with increased serum calcium concen-trations. In dogs, normocalcemic hypercalciuria is thought toresult from either intestinal hyperabsorption of calcium (so-called absorptive hypercalciuria), or decreased renal tubularreabsorption of calcium (so-called renal-leak hypercalciuria)(Table 40-4). Absorptive hypercalciuria is characterized byincreased urine calcium excretion and urine calcium concentra-tion, normal serum calcium concentration and normal or lowserum PTH concentration. Because absorptive hypercalciuriadepends on dietary calcium, urine calcium excretion and urinecalcium concentration are normal or significantly reduced dur-ing the fasting state. However, urine calcium excretion andurine calcium concentration typically increase during non-fast-ing conditions. Mean 24-hour urine calcium excretion in 33normal beagles was 0.32 ± 0.2 mg/kg body weight/day duringfasting and 0.51 ± 0.3 mg/kg body weight/day when dogs con-sumed a standard fooda (Lulich et al, 1991a). By comparison,mean urine calcium excretion in five miniature schnauzers withcalcium oxalate urolithiasis and absorptive hypercalciuria was1.0 ± 0.5 mg/kg body weight/day during fasting and 2.84 ± 0.9mg/kg body weight/day during non-fasting urine collections(Lulich et al, 1991).

A primary defect observed in people with absorptive hypercal-ciuria is apparent intestinal hyperabsorption of calcium, whichresults in increased excretion of excess calcium in urine. In addi-tion to enhanced glomerular filtration of absorbed dietary calci-um, decreased PTH secretion results in decreased renal tubularreabsorption of filtered calcium. The same phenomenon appearsto occur in dogs with absorptive hypercalciuria.

Primary intestinal abnormalities of calcium absorption, dis-orders of 1,25-vitamin D production and hypophosphatemia-induced hypervitaminosis D have been recognized as causes ofhypercalciuria in people (Park and Pearle, 2007). Absorptivehypercalciuria in people has recently been further subclassifiedas to whether increased calcium excretion is food unresponsive(Type 1) or food responsive (Type II). The underlying mecha-nism(s) of absorptive hypercalciuria has not been identified in

dogs. However, hypophosphatemia or elevated levels of 1,25-vitamin D were not observed in five dogs with absorptivehypercalciuria.

In human studies, renal-leak hypercalciuria and resorptivehypercalciuria have been documented, but have been recog-nized less frequently than excessive intestinal absorption of cal-cium. The defect with renal-leak hypercalciuria is impairedtubular reabsorption of calcium. Patients with renal-leak hyper-calciuria have high serum PTH concentrations. IncreasingPTH secretion counters the effect of additional calcium lost inurine and maintains normal blood calcium levels. Hyper-calcemia associated with calcium oxalate urolithiasis is the hall-mark of patients with resorptive hypercalciuria. Hypercalcemiais not a characteristic of patients with excessive intestinal ab-sorption of calcium or renal-leak hypercalciuria. An in-depthreview of the pathophysiology of hypercalciuria has recentlybeen published (Park and Pearle, 2007).

HyperoxaluriaAs described above in the discussion about dietary risk factorsinfluencing calcium oxalate urolithiasis, the effect of oxalic acidon calcium oxalate urolithiasis depends on the interactions ofcalcium and oxalic acid that occur in the lumen of the intestineand in urine. Intestinal hyperabsorption or accelerated endoge-nous synthesis of oxalic acid can result in hyperoxaluria. Inhealthy people, the majority of urine oxalic acid is derived fromthe endogenous metabolism of ascorbic acid, glycine, glyoxylateand tryptophan. The daily quantity of endogenously producedoxalic acid is apparently minimal. In people, hyperoxaluria hasbeen associated with inherited abnormalities of excessive oxalicacid synthesis (primary hyperoxaluria), increased consumptionof foods containing high quantities of oxalic acid or oxalic acidprecursors (Table 40-3), pyridoxine deficiency and disordersassociated with fat absorption (Williams and Smith, 1983). Wecould not find any reports of inherited hyperoxaluria or hyper-oxaluria associated with intestinal resection and fat malabsorp-tion in dogs. However, increases in urine oxalic acid excretionhave been recognized in kittens fed pyridoxine-deficient foods(Bai et al, 1989).

In people, approximately 10 to 20% of urine oxalic acid is


Table 40-4. Summary of distinguishing clinical manifestations for different types of hypercalciuria.

Absorptive Renal-leak Resorptive Features hypercalciuria hypercalciuria hypercalciuria Serum calcium Normal Normal IncreasedSerum parathyroid hormone Decreased/normal Increased IncreasedSerum phosphorus Normal/increased Normal Decreased/increased*Urine calcium

Fasting Normal Increased IncreasedDx food** Increased Increased Increased

Urine oxalic acid Normal Normal NormalUrine uric acid Normal Normal NormalBone density Normal Decreased DecreasedCalcium balance (total body) Positive Negative Negative*Phosphorus is retained in serum as glomerular filtration rate declines.**Dx food = diagnostic food used in the evaluation of normal dogs and those with calcium oxalate uroliths.

absorbed from dietary ingredients. Urine oxalic acid excretion isinversely related to dietary intake of calcium. In the intestinaltract, oxalic acid complexes with calcium and is excreted in fecesas an insoluble salt. A decrease in the combination of oxalic acidwith calcium to form calcium oxalate results in an increasedquantity of soluble oxalic acid available for intestinal absorp-tion. Therefore, it is logical to assume that urolith-formingpatients with intestinal hyperabsorption of calcium, or thoseconsuming foods with inappropriately low calcium comparedwith oxalic acid, would be at risk for increased intestinalabsorption of dietary oxalic acid, hyperoxaluria and subsequentcalcium oxalate urolith formation.

HypocitraturiaHypocitraturia is a common physiologic disturbance in peoplewith calcium oxalate urolithiasis. It has been reported to affect20 to 60% of calcium stone formers (Hamm and Hering-Smith, 2002). Urine citric acid is a negative anion that com-bines with cationic calcium, thus reducing the quantity of cal-cium available to complex with oxalic acid. Calcium citrate ismore soluble than calcium oxalate. Citrate is also a buffer, andas such, minimizes the formation of calcium phosphate. Citratealso directly inhibits crystallization and aggregation of calciumoxalate and calcium phosphate (Park and Pearle, 2007).

The role of low urine citric acid concentration in the etiolo-gy of canine calcium oxalate urolithiasis is not completely re-solved. Hypocitraturia has been observed in dogs with calciumoxalate uroliths; however, mechanisms responsible for de-creased urine citric acid excretion in dogs are as yet unknown.It is known that acid-base homeostasis influences the quantityof citric acid excreted in urine (Simpson, 1983). In normaldogs, acidosis is associated with decreased urine citric acid for-mation and excretion, whereas alkalosis promotes urine citricacid formation and excretion.

Several abnormalities associated with acidosis may lead tohypocitraturia. Examples include distal renal tubular acidosis,chronic diarrhea associated with systemic acidosis and exces-sive consumption of animal protein, which produces excessacid and promotes bone demineralization. A recent study of ahigh-protein, low-carbohydrate diet typified by the so-calledAtkins diet revealed a significant reduction in urinary pH andcitrate during the induction and maintenance phases of thediet (Reddy et al, 2002). Hypocitraturia may also occur inassociation with thiazide-induced hypokalemia, which pro-duces intracellular acidosis. Idiopathic hypocitraturia may alsooccur independent of acidosis.

The Role of Oxalate-Degrading BacteriaRecent studies have revealed a correlation between enteric col-onization of oxalate-degrading bacteria (ODB), mainlyOxalobacter formigenes, and the absence of hyperoxaluria and/orcalcium oxalate formation in rats and people (Sidhu et al, 1999;Troxel et al, 2003). Consider the following evidence: 1) Usinga rat model, one group of investigators demonstrated a rapidreversal of hyperoxaluria after probiotic administration of O.formigenes (Sidhu et al, 2001). 2) Oral administration of O.

formigenes to people with Type 1 hyperoxaluria reduced theoxalate concentration in plasma and urine (Hoppe et al,2006). 3) In rats, O. formigenes colonization induced colonicsecretion/excretion of endogenous oxalate and was associatedwith reduced oxalate levels in plasma (Hatch et al, 2006).These studies indicate that colonization of ODB in the gas-trointestinal (GI) tract can prevent enteric absorption of oxal-ic acid and increase fecal excretion of endogenously producedoxalate. ODB possess two enzymes, formyl CoA transferaseand oxalate CoA decarboxylase, that metabolize oxalic acid toformate and CO2 (Lung et al, 1994; Sidhu et al, 1997). Inaddition, O. formigenes carries a specialized membrane trans-porter, oxalate/formate antiporter, to transport the substrateand product across the membrane (Ruan et al, 1992). O.formigenes, Lactobacillus spp., Bifidobacterium lactis, Entero-coccus faecalis and Eubacterium lentum are major ODB foundin mammalian GI tracts (Allison et al, 1986; Federici et al,2004; Hokama et al, 2000; Ito et al, 1996; Weese et al, 2004).O. formigenes, an anaerobe, is solely dependent on oxalate asan energy source. It is considered to efficiently degradeoxalate in the GI tract of rats, sheep, pigs and people (Allisonet al, 1985, 1986; Daniel et al, 1987).

There have been few studies reported in which ODB havebeen evaluated in dogs in context of calcium oxalate uroliths.Oxalate-degrading Lactobacillus spp. are present in healthydogs and cats (Weese et al, 2004). However, the effect ofintestinal colonization with ODB on urine oxalate excretionhas apparently not been investigated. Oxalate-degrading bac-terial activity in canine feces has been demonstrated (Danielet al, 1987). However, the role of ODB in the pathogenesis ofcanine and feline calcium oxalate urolithiasis apparently hasnot been reported.

Considering the current evidence derived from human androdent models, we hypothesize that decreased concentrations ofintestinal ODB are a likely risk factor for calcium oxalateurolith formation in dogs and cats (Lulich et al, 2008). We alsohypothesize that the prevalence of ODB in the intestine ofdogs with calcium oxalate uroliths is lower than in clinicallyhealthy dogs without uroliths. If our hypothesis is correct,administration of novel probiotics that deliver viable ODB tothe intestine and subsequent colonization of the intestinalmucosa with O. formigenes should minimize calcium oxalateurolith recurrence.

Macromolecular Crystal Growth InhibitorsIn addition to urine concentration of lithogenic minerals andother ions, large molecular weight glycoproteins in urine pro-foundly enhance solubility of calcium oxalate. One such proteincalled nephrocalcin minimizes calcium oxalate crystal growthin human urine (Nakagawa et al, 1983). In studies of nephro-calcin obtained from urolith-forming patients, this crystalliza-tion inhibitor lacked appropriate quantities of carboxyglutamicacid residues and was unable to prevent crystal growth.Preliminary studies of urine obtained from dogs with calciumoxalate uroliths have revealed that nephrocalcin also lacksappropriate numbers of carboxyglutamic acid residues com-


pared with nephrocalcin isolated from normal canine urine(Carvalho et al, 2006).

Tamm-Horsfall glycoprotein and glycosaminoglycans inhib-it calcium oxalate crystal aggregation. One hypothesis is thatthe mechanism of action of these proteins is to block growthsites on crystals, thereby inhibiting formation of calcium oxalateuroliths (Deganello, 1993).

BIOLOGIC BEHAVIOR

Calcium oxalate uroliths may be voided in the urine or becomelodged in any portion of the urinary tract. Uroliths that remainin the urinary tract may continue to grow slowly or may becomeinactive (no further growth). Not all persistent uroliths are asso-ciated with clinical signs. Unlike infection-induced struviteuroliths, most calcium oxalate uroliths are not associated withurinary tract infection (UTI). Uroliths composed of the dihy-drate salt of calcium oxalate appear to be less likely to causecomplete urinary obstruction because of their irregular surfacecontour. Their jagged surface may prevent them from forminga continuous seal within the lumen of the urethra. However, ifuroliths remain in the urinary tract, dysuria, UTI, partial ortotal urinary obstruction and polyp formation are potentialsequelae. Spontaneous dissolution of calcium oxalate uroliths indogs has apparently not been reported.

In a retrospective clinical survey of 438 dogs surgicallytreated for urolithiasis, 111 patients had 155 known recur-rences (Brown et al, 1977). Recurrence was observed in 25%of dogs with calcium oxalate uroliths. We performed two ret-rospective studies and found that the rate of recurrence of cal-cium oxalate uroliths increased with the length of time thatdogs were evaluated: 3% recurred after three months, 9% aftersix months, 36% after one year, 42% after two years and 48%after three years (Lulich et al, 1992a). The second study eval-uated urolith recurrence in Bichon Frise dogs. After one year,37% had their first recurrence; after two years, 64% had theirfirst recurrence and 8% had their second recurrence; afterthree years, 90% had their first recurrence, 15% had their sec-ond recurrence and 4% had their third recurrence. Urolithrecurrence was detected in 100% of dogs evaluated at or afterfour years (Lulich et al, 2004). Owner and patient compliancewith therapy and persistence of factors responsible for urolithinitiation at the time of urolith eradication influence the fre-quency of urolith recurrence.

KEY NUTRITIONAL FACTORS

Because dissolution of calcium oxalate uroliths in dogs has notbeen reported, the focus of dietary management is to prevent cal-cium oxalate urolith recurrence. The goals of dietary preventioninclude: 1) reducing calcium concentration in urine, 2) reducingoxalic acid concentration in urine, 3) promoting high concentra-tion and activity of inhibitors of calcium oxalate crystal growthand aggregation in urine and 4) reducing concentration of urine.

Certain dietary excesses and deficiencies have been recog-

nized as potential risk factors for calcium oxalate urolithiasisand are the basis of key nutritional factors. Table 40-5 summa-rizes the key nutritional factors for calcium oxalate prevention.

WaterDogs consuming dry commercial foods may be at greater riskfor urolithiasis than dogs consuming moist foods because dryfoods are often associated with higher urine concentrations ofcalcium and oxalic acid and more concentrated urine.Therefore, consider moist foods, rather than dry foods, to aid inthe prevention of recurrence of calcium oxalate uroliths. Waterintake should be encouraged to achieve a urine specific gravityless than 1.020. In addition to decreasing urine specific gravity,increased water intake is likely to be associated with increasedvoiding frequency. Frequent voiding reduces crystal retentiontime thereby minimizing crystal growth.

ProteinIngestion of foods that contain high quantities of animal pro-tein may contribute to calcium oxalate urolithiasis by increasingurine calcium excretion and decreasing urine citrate excretion(Breslau et al, 1988; Lekcharoensuk et al, 2002, 2002a). Someof these consequences result from obligatory acid excretionassociated with protein metabolism. Hypercalciuria occurs innormal dogs fed high-protein foods (40% dry matter [DM]).Therefore, excessive dietary protein consumption should beavoided in dogs with active calcium oxalate urolithiasis. Therecommended range for dietary protein is 10 to 18% DM. The


Table 40-5. Key nutritional factors for foods for prevention ofcalcium oxalate uroliths.

Factors Recommended levelsWater Water intake should be encouraged to

achieve a urine specific gravity <1.020Moist food will increase water consump-tion and formation of less concentratedurine

Protein Avoid excess dietary proteinRestrict dietary protein to 10 to 18% drymatter (DM)

Calcium Avoid excess dietary calcium, especiallydietary supplements given independent ofdietRestrict dietary calcium to 0.4 to 0.7% DM

Oxalate Avoid foods high in oxalic acid (Table 40-3)Phosphorus Avoid phosphorus deficiency and maintain

a normal Ca:P ratio (1.1:1 to 2:1)Dietary phosphorus should be in the rangeof 0.3 to 0.6% DM

Sodium Recommend moderate dietary sodiumrestrictionDietary sodium should be <0.3% DM

Magnesium Avoid excess or deficient dietary magnesium Dietary magnesium should be in the rangeof 0.04 to 0.15% DM

Ascorbic acid Avoid pet foods, supplements or human(vitamin C) foods that contain ascorbic acidUrinary pH Avoid acidifying foods

Foods should produce a urinary pH 7.1-7.5

minimum recommended allowance for protein in foods forhealthy adult dogs is 10% DM (NRC, 2006).

Calcium and Oxalic AcidReduction of dietary calcium appears to be a logical therapeu-tic goal because intestinal hyperabsorption of calcium hasbeen identified as one mechanism promoting hypercalciuriain dogs with calcium oxalate uroliths. However, reducing con-sumption of calcium may increase the availability of oxalicacid for intestinal absorption and subsequent urinary excre-tion. As in the urinary bladder, calcium and oxalic acid in theintestinal lumen form a relatively insoluble complex, therebypreventing the absorption of one another. This provides aplausible explanation as to why an epidemiologic study evalu-ating risk factors for calcium oxalate urolith formation in peo-ple unexpectedly discovered that foods with higher calciumlevels were associated with reduced risk for urolith formation(Curhan et al, 1993, 1997; Curhan, 2007). Therefore, inhypercalciuric patients, reduction in dietary calcium should beaccompanied by an appropriate reduction in dietary oxalic

acid (Tables 40-3 and 40-6) (Lulich et al, 2001). The increasein the urine concentration of oxalic acid can be prevented byconcomitantly reducing calcium and oxalic acid in the food.Caution: severe calcium restriction should be avoided to pre-vent negative calcium balance. The minimum requirement forcalcium in foods for healthy dogs is 0.2% DM and the mini-mum recommended allowance is 0.4% DM (NRC, 2006). Forprevention of recurrence of calcium oxalate uroliths, reducedietary calcium to 0.4 to 0.7% DM.

People with calcium oxalate uroliths are often cautioned toavoid milk and milk products because the carbohydrate compo-nent (lactose) of these products may augment intestinal absorp-tion of calcium from any dietary source (Leman et al, 1969).Likewise, they are often discouraged from consuming foodscontaining relatively high quantities of oxalic acid (Table 40-3).Although there is agreement that excessive consumption of cal-cium and oxalic acid should be avoided, the consensus of urol-ogists is that it is inadvisable to restrict dietary calcium unlesspersistent absorptive hypercalciuria has been documented.Even then, only moderate restriction is advocated to minimizedevelopment of negative calcium balance.

PhosphorusStudies of laboratory animals, dogs and people suggest thatdietary phosphorus should not be overly restricted in patientswith calcium oxalate urolithiasis because reduction in dietaryphosphorus is often associated with augmentation of intestinalcalcium absorption and hypercalciuria (Brautbar et al, 1979). Ifcalcium oxalate urolithiasis is associated with hypophospha-temia and normal serum calcium concentration, oral phospho-rus supplementation should be considered. However, cautionmust be used because excessive dietary phosphorus may predis-pose hypercalciuric patients to formation of calcium phosphateuroliths.

Based on a recommended range for calcium (0.4 to 0.7%DM) in foods for calcium oxalate urolith prevention in caninepatients, dietary phosphorus levels should be in the range of 0.3to 0.6% DM with a calcium-phosphorus ratio range of 1.1:1 to2:1. The minimum recommended allowance for phosphorus infoods for healthy adult dogs is 0.3% DM (NRC, 2006).

SodiumSodium chloride can be added to food to increase thirst andurine volume. However, excess sodium increases urine calciumexcretion and therefore is a risk factor for calcium oxalate andcalcium phosphate urolithiasis, particularly if the urinary pH ishigh. For the same reason, if oral urinary alkalinizing agents areused, potassium citrate may be a better choice than sodiumbicarbonate. Supplemental sodium sources may also contributeto hypertension in salt-sensitive dogs.

In people, high dietary sodium consumption also reducesurine citrate concentration via sodium-induced bicarbonateloss. Daily urine calcium excretion of normal dogs consum-ing foods with 0.8% DM sodium was comparable to calciumexcretion observed in dogs with calcium oxalate uroliths(Lulich, 1991). Based on this evidence, we recommend mod-


Table 40-6. Selected human foods with minimal calcium oroxalate content.

Food items Low-calcium Low-oxalate foods foods

Meats and eggs Eggs BeefPoultry Eggs

Fish and shellfish*LambPorkPoultry

Vegetables CabbageCauliflowerMushroomsPeas, greenRadishesPotatoes, white

Milk and dairy products Cheese*Milk*Yogurt*

Fruits AppleAvocadoBananaBing cherriesGrapefruitGrapes, greenMangosMelons

CantaloupeCasabaHoneydewWatermelon

Plums, green or yellowBreads, grains, nuts Almonds Bread, white

Macaroni MacaroniPretzels NoodlesRice RiceSpaghetti SpaghettiWalnuts

Miscellaneous Popcorn JelliesPreservesSoups with allowed

ingredients

*Low in oxalate, but not low in calcium content.

erate dietary restriction of sodium (<0.3% DM sodium) foractive calcium oxalate urolith formers (Lulich et al, 2001).Typically, commercial dog foods contain two to three timesthis amount. The minimum recommended allowance forsodium in foods for healthy adult dogs is 0.08% DM (NRC,2006).

MagnesiumAlthough supplemental dietary magnesium contributes to for-mation of magnesium ammonium phosphate uroliths in somespecies (cats and ruminants), urine magnesium apparentlyimpairs formation of calcium oxalate crystals (Finco et al, 1985;Kallfez et al, 1986; Meyer and Smith, 1969).Therefore, supple-mental magnesium has been used in human patients in anattempt to minimize recurrence of calcium oxalate uroliths(Melnick et al, 1971). However, increased urine excretion ofcalcium by normal dogs given supplemental magnesium hasbeen observed. Urine calcium excretion was 0.5 ± 0.2 mg/kgbody weight/day in six normal dogs consuming a food contain-ing 0.03% DM magnesium vs. 2.65 ± 1.7 mg/kg bodyweight/day when the same dogs consumed a food containing0.38% DM magnesium (Lulich, 1991a). Pending further stud-ies, dietary magnesium restriction or supplementation is notrecommended for treatment of canine calcium oxalate uroliths.A range of 0.04 to 0.15% DM is recommended.The minimumrecommended allowance for magnesium content of foods forhealthy adult dogs is 0.06% DM (NRC, 2006).

Ascorbic Acid (Vitamin C)Supplemental ascorbic acid (a precursor of oxalate) should beavoided.

Urinary pHUrinary pH in healthy subjects reflects the acid load (acidifyingeffects) of a food. Although formation of acidic urine is desir-able for management of struvite uroliths, foods that promoteacidic urine promote hypercalciuria and hypocitraturia. There-fore, consumption of foods that result in formation of acidicurine enhances the risk of calcium oxalate urolithiasis in suscep-tible dogs. Thus, for prevention of calcium oxalate uroliths, theurinary pH should not be less than 7.0.

A recent study of a high-protein, low-carbohydrate food typ-ified by the so-called Atkins diet revealed a significant reduc-tion in urinary pH and citrate during the induction and main-tenance phases of the diet (Reddy et al, 2002).

Urine Alkalinizing AgentsDosage of urine alkalinizing agents should be individualizedfor each patient, depending on the status of the patient andpretreatment urinary pH values. Although sodium bicarbon-ate is a readily available urine alkalinizer, at recommendeddoses, (25 to 50 mg/kg body weight q12h), it provides a sig-nificant increase in sodium intake. Also, sodium may com-bine with uric acid to form sodium urate. In people, uratesalts may serve as a nidus for calcium oxalate urolith forma-tion. For these reasons, we prefer potassium citrate. Potas-

sium citrate in wax matrix tablets (Urocit-Kb), as a liquid(Polycitra-Kc) or as chewable tablets (K-CIT-Vd) may begiven. An initial dose of 40 to 75 mg/kg body weight q12h isrecommended. The final dose should be individualized basedon patient response. Potassium citrate should be adminis-tered with meals to reduce gastric irritation. Divided dosesshould be administered to maintain a consistently nonacidicenvironment in the urinary tract. Additional supplementa-tion is usually unnecessary when feeding foods (e.g.,Prescription Diet u/d Canine canned) containing adequatequantities of potassium citrate.

The goal of treatment with urine alkalinizing agents is tomaintain a urinary pH between 7.1 to 7.5. Higher values (>7.5)should be avoided until it is determined whether or not highurinary pH is a significant risk factor for formation of calciumphosphate uroliths. Owners may monitor urinary pH with pHpaper or handheld “pocket” pH meters.

OTHER NUTRITIONAL FACTORS

Pyridoxine (Vitamin B6)A deficiency of pyridoxine should be avoided because vitaminB6 promotes endogenous production of oxalic acid (Smith,1992). Pyridoxine increases the transamination of glyoxylate,an important precursor of oxalic acid, to glycine. Ex-perimentally induced pyridoxine deficiency resulted in renalprecipitation of calcium oxalate and hyperoxaluria in kittens(Bai et al, 1989). Commercial foods routinely fortified withvitamin supplements would not be deficient in pyridoxine orother vitamins. However, a homemade food might be defi-cient in pyridoxine if a multivitamin supplement is not added.Because the ability of supplemental pyridoxine (above nutri-tional requirements) to reduce urine oxalic acid excretion indogs is unknown, there is insufficient evidence to recommendor abandon this practice. The minimum recommendedallowance for pyridoxine in foods for healthy dogs is 1.5mg/kg DM (NRC, 2006).

Vitamin DExcessive levels of vitamin D (which promote intestinalabsorption of calcium) in foods for patients at risk for calciumoxalate urolithiasis should be avoided. Commercial foods aretypically replete with vitamin D and should not be further sup-plemented. Excessive supplementation of homemade foodswith vitamin D could also pose a risk. For prevention of calci-um oxalate urolithiasis, restrict vitamin D in foods to between500 to 1,500 IU/kg DM. The recommended minimumallowance for foods for healthy adult dogs is 552 IU/kg DM(NRC, 2006).

FEEDING PLAN

Although struvite, urate and cystine uroliths dissolve whenurine is no longer supersaturated with lithogenic substances,dissolution of calcium oxalate uroliths in dogs has not been


reported. Therefore, only physical methods are currently avail-able for removing clinically active calcium oxalate uroliths.Surgery is the time-honored method to remove calcium oxalateuroliths from the urinary tract; however, complete surgicalremoval of all visible uroliths may be difficult because of theirsmall size and irregular contour. Small urocystoliths may beaspirated through a transurethral catheter (Figure 38-6)(Lulich and Osborne, 1992) or removed by voiding urohy-dropropulsion (Figure 38-5 and Table 38-7) (Lulich et al,1993). Extracorporeal lithotripsy also provides a nonsurgicalmeans of treating some dogs with calcium oxalate nephrolithsand/or ureteroliths (Adams and Senior, 1999). We have hadsuccess fragmenting calcium oxalate urocystoliths and ure-throliths with intracorporeal laser lithotripsy.

In some patients, calcium oxalate uroliths are clinically silent,obviating the need for intervention. For patients in which inter-vention is not warranted, the status of uroliths should be peri-odically assessed by urinalyses, renal function tests and radiog-raphy or ultrasonography. (See Reassessment below.)

Dietary and medical dissolution of calcium oxalate uroliths

in dogs has not been reported. However, there is a role fordietary management in prevention of calcium oxalate urolithrecurrence. In general, dietary and medical therapy should beimplemented in stepwise fashion, with the initial goal ofreducing the urine concentration of lithogenic substances(Table 40-7). Medications that have the potential to induceunwanted, sustained, detrimental alterations in the composi-tion of metabolites should be reserved for patients with activeor frequently recurring calcium oxalate uroliths. Cautionshould be used to ensure that side effects of treatment are notmore detrimental than the effects of uroliths. The cause ofhypercalcemia (e.g., primary hyperparathyroidism) should becorrected in patients with hypercalcemia and resorptivehypercalciuria. An attempt should be made to identify riskfactors for urolith formation in patients with normal serumcalcium concentrations (Table 40-2). Amelioration or controlof the consequences of risk factors (e.g., urine oversaturationwith lithogenic minerals) should minimize urolith growthand recurrence.

The feeding plan includes assessing and selecting the bestfood and assessing and determining the feeding method.

Assess and Select the FoodTable 40-8 compares the recommended levels of key nutri-tional factors to the key nutritional factor content of selectedcommercial veterinary therapeutic foods for calcium oxalateurolith prevention. Select the food that most closely match-es the recommended levels of key nutritional factors for pre-venting the recurrence of calcium oxalate uroliths. Becausethese foods are intended for long-term feeding, they shouldalso be approved by the Association of American Feed Con-trol Officials (AAFCO), or some other credible regulatoryagency. Dogs consuming dry commercial foods may be atgreater risk for urolithiasis than those consuming moist foodsbecause dry foods are often associated with higher urine con-centrations of calcium and oxalic acid and more concentrat-ed urine. When possible, moist foods should be selected.

Dogs with calcium oxalate urolithiasis frequently consumehuman food. Calcium oxalate is the most common urolithtype recognized in people living in developed countries. Aspeople feed their dogs the same dietary proportions andingredients they feed themselves, it is logical to assume thatdogs would be exposed to the same nutritional risk factors forurolith formation (Tables 40-2 and 40-3). Therefore, feedinghuman foods with high levels of calcium and oxalic acidshould be avoided.

In addition to consumption of human food, an associationbetween calcium oxalate urolithiasis and consumption ofcommercially available treats has been noted. The high sodi-um content of some commercial dog treats may help explainthis association because sodium consumption promoteshypercalciuria (Lulich et al, 1992). Like foods, treats shouldnot contain more than 0.3% DM sodium and they should belimited to less than 10% of the total food regimen (volume orweight basis).

Feeding foods designed to dissolve struvite uroliths provides


Table 40-7. Recommendations for the management of calciumoxalate urolithiasis in dogs.

1. Obtain data (postsurgical radiography, complete urinalysis,serum concentrations of calcium, urea nitrogen and creati-nine) to evaluate effectiveness of renal function, calciumhomeostasis, surgery, voiding urohydropropulsion or lithotripsy.

2. If the dog is hypercalcemic, correct underlying cause.3. If the dog is normocalcemic, consider foods with reduced

calcium, oxalate, sodium and protein that do not promoteformation of acidic urine. Ideally foods should contain addi-tional water and citrate and have adequate phosphorus andmagnesium. Avoid excess and/or supplemental vitamins Cand D. Prescription Diet u/d Canine or w/d Canine* is oftenrecommended.

4. Reevaluate patient in two to four weeks to verify dietary compliance (urine specific gravity and pH and serum ureanitrogen concentration) and amelioration of crystalluria (urinesediment examination).

5. Consider additional potassium citrate if calcium oxalate crystals and aciduria persist.

6. Reevaluate patient in two to four weeks to verify dietary compliance (urine specific gravity and pH and serum ureanitrogen concentration) and amelioration of crystalluria (urinesediment examination). Consider vitamin B6 supplementation(2 to 4 mg/kg body weight q24 to 48 hours) if calciumoxalate crystalluria persists.

7. Again, reevaluate patient in two to four weeks to verifydietary compliance and amelioration of crystalluria. Consideradministration of hydrochlorothiazide (2 mg/kg body weightq24 to 48 hours) if calcium oxalate crystalluria persists.Adverse effects of hydrochlorothiazide administration includedehydration, hypokalemia and hypercalcemia.

8. After three to six months, reevaluate patient to verify dietarycompliance and amelioration of crystalluria. Check for urolithrecurrence by abdominal radiography. If no uroliths arepresent, continue current therapy and reevaluate in three to six months. If uroliths have recurred, consider voiding urohydropropulsion (Figure 38-5 and Table 38-7), or lithotrip-sy. If unsuccessful and clinical signs referable to urocystolithsare persistent, consider surgery. Continue therapy to mini-mize urolith growth if clinical signs are not present.

*Hill’s Pet Nutrition, Inc., Topeka, KS, USA.

some benefits, but also presents several risks to patients withcalcium oxalate uroliths (Table 40-2). The lower protein con-tent and potential to enhance formation of less concentratedurine promote reduction of calcium and oxalic acid concentra-tions in urine. Although formation of acidic urine is desirablefor management of struvite uroliths, foods that promote acidicurine promote hypercalciuria and hypocitraturia. Therefore,consumption of struvite litholytic foods that result in formationof acidic urine enhances the risk of calcium oxalate urolithiasisin susceptible dogs. Likewise, aggressive reduction of dietaryphosphorus may also promote hypercalciuria. If struvite uro-liths occur in breeds of dogs commonly affected with calciumoxalate uroliths, patients should be evaluated for calcium ox-alate crystalluria after initiating dietary therapy designed to pre-vent struvite urolith formation. If calcium oxalate crystalluriapersists, alternate methods of preventing struvite urolithsshould be considered.

Another criterion for selecting a food that may becomeincreasingly important in the future is evidence-based clinicalnutrition. Practitioners should know how to determine risksand benefits of nutritional regimens and counsel pet ownersaccordingly. Currently, veterinary medical education and con-tinuing education are not always based on rigorous assessmentof evidence for or against particular management options. Still,studies have been published to establish the nutritional benefitsof certain pet foods. Chapter 2 describes evidence-based clini-cal nutrition in detail and applies its concepts to various veteri-nary therapeutic foods.

Assess and Determine the Feeding MethodTransitioning the patient from its current food to a calciumoxalate urolith preventive food should be done gradually overseveral days. Begin the transition by feeding 75% of the currentfood and 25% of the new food on Day 1. On Day 2 feed halfof each food. On Day 3 feed 75% as the new food. By Day 4 or5, feed only the new food.

Because moist foods are recommended to increase water

intake and production of less concentrated urine, specificamounts (meal fed) should be fed two to three times per dayrather than free-choice feeding. Moist foods can spoil if leftuneaten at room temperature for several hours (Chapter 11).Opened containers of moist foods should be refrigerated andthe feeding bowl should be kept clean.

Besides offering moist foods, several additional approachesmay facilitate increased water intake. First, ensure multiplebowls are available in prominent locations in the dog’s environ-ment; this may mean providing several bowls outside in a largeenclosure or a bowl on each level of the house. Second, bowlsshould be clean and always be filled with fresh water. Third,small amounts of flavoring substances (e.g., salt-free bouillon)can be added to water sources. Fourth, ice cubes can be offered.Fifth, if a dry food is selected, add liberal quantities of water;however, as with moist foods, be aware that potential food safe-ty issues might arise if moistened dry foods are left uneaten forprolonged intervals at room temperature (Chapter 11).

If the patient has a normal body condition score (2.5/5 to3.5/5), the amount of the previous food being fed was probablyappropriate. On an energy basis, a similar amount of the newfood would be a good starting place.


Table 40-8. Levels of key nutritional factors in selected veterinary therapeutic foods used to minimize recurrence of calcium oxalate urolithiasis in dogs compared to recommended levels.*

Protein Calcium Phosphorus Sodium Magnesium Urinary Dry foods (%) (%)** (%)** (%) (%) pH***Recommended levels 10-18 0.4-0.7 0.3-0.6 <0.3 0.04-0.15 7.1-7.5Hill’s Prescription Diet u/d Canine 11.2 0.34 0.15 0.23 0.046 7.70Medi-Cal Urinary SO 13 16.7 1.0 0.6 1.3 0.2 5.5-6.0Purina Veterinary Diets NF KidNey Function 15.9 0.76 0.29 0.22 0.07 6.7-7.5Royal Canin Veterinary Diet Urinary SO 14 17.0 0.80 0.63 1.38 0.066 5.5-6.0

Protein Calcium Phosphorus Sodium Magnesium Urinary Moist foods (%) (%)** (%)** (%) (%) pH***Recommended levels 10-18 0.4-0.7 0.3-0.6 <0.3 0.04-0.15 7.1-7.5Hill’s Prescription Diet u/d Canine 13.3 0.35 0.17 0.28 0.049 7.4Medi-Cal Urinary SO 18.7 1.0 0.8 1.1 0.10 5.5-6.0Purina Veterinary Diets NF KidNey Function 16.5 0.50 0.30 0.24 0.08 6.7-7.5Royal Canin Veterinary Diet Urinary SO 18.5 0.97 0.86 1.45 0.059 5.5-6.0*Manufacturers’ published values. Nutrients expressed as % dry matter, unless otherwise stated; moist foods are best; avoid foods withadded vitamin C (ascorbic acid); avoid foods with high oxalate ingredients (Table 40-3).**Calcium-phosphorus ratio should be in the range of 1.1:1 to 2:1.***Protocols for measuring urinary pH may vary.

Table 40-9. Expected changes associated with dietary andmedical therapy to minimize recurrence of calcium oxalateuroliths.

Factors Pre-therapy Prevention therapyPolyuria ± VariablePollakiuria 0 to 4+ 0Hematuria 0 to 4+ 0Urine specific gravity Variable 1.004-1.015Urinary pH <7.0 >7.0Pyuria 0 to 4+ 0Calcium oxalate crystals 0 to 4+ 0Bacteriuria 0 to 4+ 0Bacterial culture of urine 0 to 4+ 0Urea nitrogen (mg/dl) >15 <15Urolith size and number Small to large 0

ADJUNCTIVE MEDICAL MANAGEMENT

Citric AcidCitric acid forms soluble salts with calcium thereby mini-mizing calcium oxalate crystal formation (Nicar et al, 1987).Citric acid is also beneficial because it is metabolized tobicarbonate and promotes formation of alkaline urine (Ba-ruch et al, 1975). In dogs, chronic metabolic acidosis inhibitsrenal tubular reabsorption of calcium, whereas metabolicalkalosis enhances tubular reabsorption of calcium (Suttonet al, 1979). Potassium citrate is preferred to sodium bicar-bonate as an alkalinizing agent because oral administrationof sodium enhances urine calcium excretion. If persistentaciduria or hypocitraturia is recognized (mean urine citrate

excretion of 33 normal beagles was 2.57 ± 2.31 mg/kg bodyweight/day), therapy with wax matrix tablets of potassiumcitrate (Urocit-K) should be considered. Alternatively, a liq-uid product (Polycitra-K) may be given to small dogs.Chewable treats containing potassium citrate (K-CIT-V)are also available. An initial dose of 40 to 75 mg/kg bodyweight q12h is recommended. The final dose should bebased on patient response. Potassium citrate should beadministered with meals to reduce gastric irritation. Whenfeeding foods with adequate quantities of potassium citrate,additional supplementation is often not needed.

Thiazide DiureticsThiazide diuretics have been recommended to reduce recur-rence of calcium-containing uroliths in people because of their


Table 40-10. Managing highly recurrent calcium oxalate uroliths.

Causes Identification Therapeutic goalClient and patient causesInadequate dietary compliance Question owner Emphasize need to feed dissolution food

Persistent calcium oxalate crystalluria exclusivelyUrea nitrogen >10-15 mg/dlUrine specific gravity >1.010-1.020Urinary pH <7.0-7.5 during treatment with Prescription Diet u/d Canine* (use lower values for the canned food)

Administration of vitamin-mineral Question owner Discontinue vitamin-mineral supplementssupplements containing calcium and vitamins C and DClinician factorsIncomplete surgical removal of uroliths Postsurgical radiography revealing uroliths Uroliths not causing clinical signs should be

Persistence of clinical signs after cystotomy monitored for potentially adverse or recurrence of clinical signs soon after consequences (obstruction, urinary tractcystotomy (within one to three months) infection, etc.)

Clinically active uroliths may require surgicalremovalRemove small uroliths by voiding urohy-dropropulsion or lithotripsy

Inappropriate food choice Persistent calcium oxalate crystalluria Choose foods with reduced levels of calcium, oxalic acid, protein and sodium thatdo not promote formation of acidic urineConsider adding potassium citrate if aciduria persists

Inadequate monitoring Postsurgical radiography to verify complete Perform postsurgical radiography to urolith removal was not performed evaluate success of surgeryUrinalysis or urine sediment examinations Perform complete urinalysis within one towere not performed within three to six three months of initiation of therapymonths of initiation of therapy Once stable, urinalysis should be

performed every four to six monthsPerform survey lateral abdominal radiography every four to six months toassess recurrence

Corticosteroid administration Corticosteroids were prescribed to manage If possible, discontinue corticosteroid other disease conditions administration

Disease factorsHypercalcemia Elevated serum calcium concentration Identify and, if possible, eliminate underlying

cause for hypercalcemia (hyperparathy-roidism, neoplasia, hypervitaminosis D, etc.)

Recurrence of uroliths despite Lateral radiograph of abdomen Uroliths not causing clinical signs should appropriate management be monitored for potentially adverse

consequences (obstruction, urinary tract infection, etc.)Clinically active uroliths may require surgical removalRemove small uroliths by voiding urohydropropulsion or lithotripsy

*Hill’s Pet Nutrition, Inc., Topeka, KS, USA.


Figure 40-2. Algorithm for dietary and medical management of calcium oxalate uroliths in dogs.


ability to reduce urine calcium excretion (Churchill and Taylor,1985). However, they should only be considered for patientswith severe hypercalciuria. A beneficial reduction in urine cal-cium excretion in dogs with calcium oxalate urolithiasis hasbeen observed following administration of hydrochlorothiazide(2 to 4 mg/kg body weight q12h) for two weeks. However, areduction in urine calcium excretion was not detected followinghydrochlorothiazide administration (20 to 65 mg/kg bodyweight q12h) to clinically healthy beagles (Lulich, 1991b).Results of a short-term study of the effects of hydrochlorothi-azide on calcium excretion in the urine of adult dogs with nat-urally occurring calcium oxalate urolithiasis revealed thathydrochlorothiazide significantly reduced urine calcium con-centration (Lulich et al, 2001). The greatest reduction in urinecalcium concentration and excretion was achieved when dogsreceived hydrochlorothiazide and a urolith prevention diet.Thiazide diuretic administration is not recommended as first-line therapy at this time. The decision to use thiazides shouldbe accompanied by owner informed consent and appropriateclinical and laboratory monitoring for early detection of adverseeffects (dehydration, hypokalemia, hypercalcemia).

AllopurinolSome people who form calcium oxalate uroliths associated withmarked hyperuricosuria have benefited from allopurinol-induced reductions in the magnitude of hyperuricosuria. Weare unaware of any counterpart of this phenomenon in dogs. Incontext of this discussion, it is relevant that the end product ofpurine metabolism in people is uric acid. However in dogs, theend product of purine metabolism is the highly soluble allan-toin. Therefore, we do not recommend that allopurinol be con-sidered for dogs that form calcium oxalate uroliths.

REASSESSMENT

The goal of therapy is to minimize calcium oxalate urolithrecurrence (Figure 40-2). However, this expectation may beunrealistic because the primary causes responsible for urolith

formation are multifactorial and incompletely understood.With the information and techniques currently available, how-ever, veterinarians can minimize urolith recurrence and preventthe need for additional surgical removal of uroliths by appropri-ate monitoring and intervention.

Therapy should be initiated in a stepwise fashion (Table 40-7). If therapy is effective and clients remain compliant, dietaryand pharmacologic management should result in formation ofless concentrated urine without calcium oxalate crystalluria(Table 40-9). Strive to achieve urine specific gravity values lessthan 1.020. After this is achieved, a urinalysis and survey later-al abdominal radiographs should be performed every two tofour months. Dietary and pharmacologic changes should beconsidered if crystalluria or concentrated urine persist (Table40-10). These recommendations should facilitate detection ofrecurrent urocystoliths by radiography when they are smallenough to remove by voiding urohydropropulsion (Figure 38-5and Table 38-7). Likewise, urethroliths may be fragmented byintracorporeal laser lithotripsy. Nephroliths may be fragmentedby extracorporeal shockwave lithotripsy. After the frequency ofurolith recurrence has been established, the frequency of evalu-ation can be modified such that predicted recurrences can bediagnosed and managed accordingly.

ENDNOTES

a. Prescription Diet k/d Canine. Hill’s Pet Nutrition, Inc.,Topeka, KS, USA.

b. Urocit-K. Mission Pharmacal, San Antonio, TX, USA.c. Polycitra-K. Willen Drug Co., Baltimore, MD, USA.d. K-CIT-V. V.E.T. Pharmaceuticals, Inc., Fenton, MO, USA.

REFERENCES

The references for Chapter 40 can be found at www.markmorris.org.

CASE 40-1

Urine Dribbling in a Yorkshire TerrierJody P. Lulich, DVM, PhD, Dipl. ACVIM (Internal Medicine)

Carl A. Osborne, DVM, PhD, Dipl. ACVIM (Internal Medicine)College of Veterinary MedicineUniversity of MinnesotaSt. Paul, Minnesota, USA

Patient AssessmentA nine-year-old, neutered male Yorkshire terrier was examined for urine dribbling and depression of two days’ duration. Physicalexamination revealed that the dog was 8 to 10% dehydrated; capillary refill time was slightly delayed. The dog voided small spurtsof reddish-brown urine onto the examination table when its abdomen was palpated. The physical examination was otherwise nor-


mal. Body weight was 5 kg; the dog had a normal body condition score (3/5). Survey radiographs revealed a large urinary bladderand a radiodense urolith in the urethra at the proximal end of the os penis and several uroliths in the urinary bladder (Figure 1).

The diagnosis was urolithiasis of the lower urinary tract associated with urethral obstruction. The depression was probably a con-sequence of postrenal azotemia.

Assess the Food and Feeding MethodThe dog was fed a commercial moist adult maintenance foodtwice daily and various table foods.

Questions1. What additional assessments should be performed?2. What should be the patient’s initial treatment plan?

Answers and Discussion1. A blood sample should be submitted for biochemical analy-

sis to evaluate the degree of azotemia and detect concurrentelectrolyte abnormalities. A urinalysis and aerobic bacterialculture of the urine will help predict the mineral composi-tion of the uroliths.

2. Replacement of the patient’s fluid deficits with an appropri-ate fluid given intravenously is important. The urinary blad-der can be evacuated by decompressive cystocentesis to en-hance renal elimination of waste products. Reducing pres-sure in the urinary bladder also would facilitate retrogradeurohydropropulsion of the urethrolith.

Further AssessmentResults of laboratory tests revealed azotemia, hyperphosphatemia and hypobicarbonatemia (Table 1). Serum alkaline phosphataseactivity was also increased. Crystals were not observed by urine sediment examination and the urine culture was negative (Table 2).The urethrolith was successfully flushed into the urinary bladder by retrograde urohydropropulsion. Prophylactic antimicrobialswere administered (amoxicillin-clavulanic acid, 14 mg/kg,q12h) to prevent iatrogenic bacterial urinary tract infectionassociated with transurethral catheterization.

Additional QuestionWhat is the most likely mineral composition of these radio-dense uroliths?

Answer and DiscussionThe advantages and disadvantages of medical urolith dissolu-tion and surgical urolith removal can be more accurately as-sessed by predicting the mineral composition of uroliths. Mag-nesium ammonium phosphate (struvite), calcium oxalate, calci-um phosphate, silica and cystine uroliths can all be radiodense(Table 3). It was surmised that this patient’s uroliths were prob-ably not composed of magnesium ammonium phosphate be-cause of the breed and gender of the dog along with findings of aciduria and a negative bacterial culture. These findings suggestedthat the uroliths were not composed of struvite and therefore were not amenable to medical dissolution.

Treatment and Further AssessmentThe uroliths were surgically removed following resolution of azotemia on the third day of hospitalization (Table 1). Postsurgicalradiographs verified that all uroliths were removed. Quantitative analysis revealed that the uroliths were composed of 100% calci-um oxalate monohydrate.

Further Questions1. Outline an appropriate feeding plan (food and feeding method) for this dog.

Figure 1. Survey lateral radiograph of a nine-year-old male Yorkshireterrier revealing multiple radiodense uroliths in the urinary bladderand a radiodense urolith at the proximal end of the os penis.

Table 1. Serum biochemistry values of a nine-year-old male Yorkshireterrier with radiodense urocystoliths.*

Reference Factors values Day 1 Day 2 Day 3SUN (mg/dl) 7-28 186 141 16Creatinine (mg/dl) 0.5-1.5 6.5 1.2 0.9Calcium (mg/dl) 9.3-11.4 8.7 8.2 8.7Phosphorus (mg/dl) 1.9-7.0 19.2 3.5 3.2Sodium (mEq/l) 143-150 144 149 149Potassium (mEq/l) 3.2-5.6 4.7 3.6 3.3ALT activity (U/l) 5-62 78 ND NDAlk phos activity (U/l) 10-149 223 ND NDTotal CO2 (mEq/l) 17-26 14.5 ND ND

Key: SUN = serum urea nitrogen, ALT = alanine aminotransferase, Alk phos = alkaline phosphatase, ND = not done.*Dietary therapy was initiated on Day 14.


2. Is reassessment important for this patient?

Answers and Discussion1. Dietary therapy to prevent urolith recurrence was

initiated at the time of suture removal. Dietary rec-ommendations included reducing calcium, oxalic ac-id, protein and sodium, providing additional waterand citrate and maintaining adequate phosphorusand magnesium. A moist veterinary therapeutic food(Prescription Diet u/d Caninea) was chosen becauseits nutrient content matches this nutrient profile.This food avoids excess dietary protein, oxalic acidand calcium, and promotes formation of less concen-trated, alkaline urine. These dietary characteristicsare helpful in preventing recurrence of calcium oxa-late uroliths. The food was offered in two separatemeals each day (one-fourth can twice daily, total 375kcal [1.57 MJ]). The owners were also instructed toavoid feeding the dog any human foods, commercialdog treats and vitamin-mineral supplements (espe-cially those containing vitamins C and D and calci-um).

2. Regular reassessment is important because calciumoxalate uroliths commonly recur. Results of a retro-spective study on the recurrence rate of calciumoxalate uroliths in dogs indicated that the rate ofrecurrence increased with the length of time thatdogs were evaluated: 3% recurred after three months,9% after six months, 35% after one year, 42% aftertwo years and 48% after three years.This dog shouldbe examined (i.e., urinalysis, survey abdominal radi-ography) at regular intervals to evaluate efficacy ofmedical therapy and to detect uroliths while they aresmall enough to remove with nonsurgical tech-niques. This patient should also be evaluated forhyperadrenocorticism because of the increased se-rum alkaline phosphatase activity. Glucocorticoidadministration and hyperadrenocorticism are associ-ated with hypercalciuria and increase the risk for cal-cium oxalate urolith formation.

Progress NotesTable 2 summarizes the urinalysis results following six weeks of dietary management. Prescription Diet u/d Canine was successfulin promoting less concentrated, alkaline urine in this dog. Reassessment every three to six months was recommended to the owner.

Endnotea. Hill’s Pet Nutrition Inc., Topeka, KS, USA.

BibliographyOsborne CA, Lulich JP, Bartges JW, et al. Canine and feline urolithiasis: Relationship of etiopathogenesis to treatment and pre-vention. In: Osborne CA, Finco DR, eds. Canine and Feline Nephrology and Urology. Baltimore, MD: Williams & Wilkins, 1995;798-888.

Table 2. Urinalyses of a nine-year-old male Yorkshire terrier with radiodenseurocystoliths.*

Factors** Day 1 Day 14*** Day 28 Day 60Specific gravity 1.015 1.025 1.008 1.015pH 6.0 6.5 7.5 7.5Protein† 1+ 1+ Trace TraceRBC†† 100-150 8-12 0 1-3WBC†† 12-16 2-4 1-2 0Crystals††† None None None NoneAerobic bacterial culture Neg Neg Neg Neg

Key: RBC = red blood cells, WBC = white blood cells, Neg = negative.*Samples collected by cystocentesis.**Glucose, bilirubin and acetone were not detected in any specimen.***Dietary therapy was initiated on Day 14.†Values represent semiquantitative evaluations based on a scale of 0 to 4;urine volume was not considered.††Per high power field (x450).†††Per low power field (x100).

Table 3. The advantages and disadvantages of medical urolith dissolutionand surgical urolith removal can be accurately assessed after the mineralcomposition of the urolith is known or predicted. This table lists factors usedto predict mineral composition of radiodense uroliths when no uroliths areavailable for quantitative analysis vs. clinical findings in the patient describedin this case.*

Factors MAP CaOx CaP Silica CystineTypical urinary pH No Yes Possible Yes YesTypical

crystalluria Possible Possible Possible Possible PossibleTypical urine

culture No Yes Yes Yes YesTypical

radiographic Yes Yes Yes Yes Yesdensity

Typical radiographic Yes Yes Yes No Nocontour

Typical serumbiochemistry Yes Yes Possible Yes Yes values

Typical breed No Yes Yes No NoTypical gender No Yes Yes Yes YesTypical age No Yes Yes Yes No

Key: MAP = magnesium ammonium phosphate, CaOx = calcium oxalate,CaP = calcium phosphate.*Characteristics of urate uroliths were not considered because they are typi-cally radiolucent.

Chapter 40 · Chapter 40 Canine Calcium Oxalate Urolithiasis: Changing Paradigms in Detection,...

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