Inheritance of urinary calculi in the Dalmatian

Dalmatians are unique among dogs in that they excrete uric acid in their urine as the end product of purine metabolism rather than allantoin as do other breeds of dogs. Urinary calculi form from urate (salts of uric acid) and can cause urethral obstruction in male Dalmatians. Although all Dalmatians have the primary defect, only a subset develops clinical disease. We postulated that calculi formation might have a genetic component that segregates within the breed, causing some animals to form calculi and others to never form calculi despite excreting uric acid in their urine. We used a survey to ascertain the urinary calculi status based on clinical signs of adult Dalmatians aged 6 years or older, and we used pedigrees from these same animals to estimate the heritability of the clinical manifestation of urate calculi within the breed to be .87 (.75-.96). The prevalence of the disease was 34% (24.99-43.70%) among male Dalmatians in our survey. The high heritability of the disease makes it possible for breeders to effectively select against the disease.     

Urine metabolite values in fed and nonfed clinically normal beagles.

Twenty-four-hour excretion of urine metabolites was determined in 33 clinically normal Beagles during periods of consumption of a standard diet and when food was withheld. The goal was to determine normal canine values for urine analytes incriminated in the genesis of calcium oxalate uroliths. During periods when dogs consumed food, dairy urinary excretion of calcium, uric acid, sodium, potassium, magnesium, ammonium, and hydrogen ions were significantly (P = 0.0004, 0.0038, 0.001, 0.0001, 0.0004, 0.0001, and 0.024, respectively) higher than when food was withheld. Urinary excretion of phosphorus, oxalate, and citrate were not significantly different between samples obtained during periods of food consumption and when food was withheld. Male dogs excreted significantly higher quantities of urine oxalate than females during fed (P = 0.003) and nonfed (P = 0.003) conditions. When food was withheld, urinary uric acid excretion was significantly higher in males than females (P = 0.01). Females excreted significantly more urine calcium than males when food was withheld (P = 0.003). Our results indicated that dietary conditions influence the quantity of sodium, potassium, calcium, magnesium, and uric acid excreted in the urine of clinically normal dogs; therefore, dietary conditions should be considered when measuring the concentration of these analytes in urine.     

Dissolution of canine ammonium urate uroliths

Medical therapy that may be effective in promoting dissolution of canine ammonium urate uroliths includes the following: reduction of dietary purines, reduction in in vivo production of uric acid, and alkalinization of urine.     

Comparison of three techniques for the diagnosis of urinary tract infections in dogs with urolithiasis

OBJECTIVES: To identify an appropriate sampling technique(s) to accurately detect the bacteria causing urinary tract infections in dogs with urolithiasis. METHODS: Twenty-one dogs with urolithiasis were included in the study. Three types of samples were taken from each dog. Urine was collected by cystocentesis, and a urinary bladder mucosal biopsy and urolith were retrieved during cystotomy. The samples were then cultured on blood agar and MacConkey's agar to identify the bacteria associated with urinary tract infections. RESULTS: Bacterial urinary tract infection was found in 16 cases (76.19 per cent). The most prevalent bacteria found to cause urinary tract infection were Escherichia coli (n=7), followed by coagulase-positive Staphylococcus species (n=4), Klebsiella pneumoniae (n=2), Pseudomonas aeruginosa (n=2) and Proteus mirabilis (n=1). In the case of a positive urine culture, the same bacteria were also cultured from the urinary bladder mucosal biopsy alone or from both the urinary bladder mucosal biopsy and urolith. However, in the case of a negative urine culture, bacteria were found to be present in the urinary bladder mucosal biopsy or urolith cultures in 23.81 per cent of dogs. The uroliths that gave positive culture results were either infection-induced uroliths composed of struvite and calcium carbonate phosphate, ammonium acid urate only or metabolic uroliths composed of calcium oxalate and calcium phosphate, or calcium phosphate only. All the uroliths that gave negative culture results were metabolic uroliths composed of calcium oxalate and/or calcium phosphate, and uric acid and calcium phosphate. CLINICAL SIGNIFICANCE: When the culture from the urine obtained by cystocentesis is negative, cultures of urinary bladder mucosal biopsy and urolith are recommended in dogs with urolithiasis in order to accurately assess the microbiological status of the urinary tract.     

Canine Silica Urolithiasis

Silica "jack-stone" uroliths developed in the urinary bladder and urethra of 83 dogs living in the United States. Naturally occurring silica jack stones have not been encountered prior to 1976. German Shepherd Dogs comprised more than 1/3 of affected animals; the remainder encompassed 26 other breeds. In this series, 81 were males and 2 were females. The mean age of the dogs was 5.8 years, with a range of 1.5 to 12 years. Several observations prompt the hypothesis that development of silica uroliths may be related to diet. Although most silica uroliths had a characteristic jack-stone appearance, not all silica uroliths had a jack-stone configuration and not all jack stones were composed of silica. Some calculi were comprised of a combination of silica and struvite. Silica uroliths were radiodense, compared with adjacent tissue, but were not associated with identifiable crystals in urine. The urine pH of affected dogs varied from acid to alkaline. Silica urolithiasis recurred in 5 dogs following surgery. Urinary tract infections, when they occurred, appeared to be a sequela of silica urolithiasis. Pending further studies, management of silica uroliths should include their removal from the urinary tract and eradication of associated urinary tract infections. Prophylactic measures should include attempts to augment urine volume and change of diet.     

Feline urate urolithiasis: a retrospective study of 159 cases

The objective of the study was to characterize the signalment, clinicopathologic data, and diagnostic imaging of cats with urate urolithiasis, as well as the salts of uric acid present in the uroliths. A retrospective analysis of feline urate uroliths submitted to the GV Ling Urinary Stone Analysis Laboratory between 2000 and 2008 was included. From these data, records were assimilated from referring veterinarians (143); furthermore, all recorded cases from within the William R Pritchard Veterinary Medical Teaching Hospital (16) were included. Median values for the complete blood count and chemistry panels available were within the reference intervals, when provided, with only a few outliers present. Of all cases evaluated, seven had a portosystemic shunt (PSS). Cats with urate uroliths and a PSS were younger than cats without a PSS (2 years vs 7 years). The pathogenesis of urate uroliths in cats is poorly understood. Most cats were not completely evaluated for a PSS, however, clinicopathologic parameters indicating hepatic dysfunction were seldom noted; more sensitive diagnostics such as serum bile acids were rarely performed to confirm or negate the presence of a shunt. Studies are warranted to evaluate pathogenesis of urate uroliths to tailor proper management and breeding strategies.     

Influence of hydrochlorothiazide on urinary calcium oxalate relative supersaturation in healthy young adult female domestic shorthaired cats

Hydrochlorothiazide (1 mg/kg PO q12h) or placebo was administered to healthy cats for 2 weeks in a masked, placebo-controlled, crossover-design study, and 24-hour urine samples were collected. When cats received hydrochlorothiazide, 24-hour urine volume, ammonia, chloride, creatinine, magnesium, oxalic acid, phosphate, potassium, and sodium were significantly higher than when cats received placebo. Hydrochlorothiazide was associated with significantly lower urinary saturation for calcium oxalate, but no difference was found in 24-hour urine calcium and citrate, urinary saturation for struvite, or blood ionized calcium. Hydrochlorothiazide decreased urinary saturation for calcium oxalate and could be useful in managing cats with calcium oxalate uroliths. Results of this study, however, should not be extrapolated to cats that form calcium oxalate uroliths.     

Evaluation of urine and serum metabolites in miniature schnauzers with calcium oxalate urolithiasis.

To evaluate underlying causes of calcium oxalate urolithiasis, 24-hour excretion of urine metabolites was measured in 6 Miniature Schnauzers that formed calcium oxalate (CaOx) uroliths during periods when they were fed a standard diet and during periods when food was withheld. Serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D also were evaluated. Serum calcium concentrations were normal in all 6 affected Miniature Schnauzers; however, during diet consumption, mean 24-hour urinary excretion of calcium was significantly (P = 0.025) higher than calcium excretion when food was withheld. In 1 dog, urinary calcium excretion was lower during the period of food consumption, compared with the period when food was withheld. Compared with clinically normal Beagles, Miniature Schnauzers that formed CaOx uroliths excreted significantly greater quantities of calcium when food was consumed (P = 0.0004) and when food was withheld (P = 0.001). Miniature Schnauzers that formed CaOx uroliths excreted significantly less oxalate than clinically normal Beagles during fed (P = 0.028) and nonfed (P = 0.004) conditions. Affected Miniature Schnauzers also excreted abnormally high quantities of uric acid. Excretion of citrate was not different between Miniature Schnauzers with CaOx urolithiasis and clinically normal Beagles. In 5 of 6 Miniature Schnauzers with CaOx urolithiasis, concentrations of serum parathyroid hormone were similar to values from age- and gender-matched Miniature Schnauzers without uroliths. The concentration of serum parathyroid hormone in 1 dog was greater than 4 times the mean concentration of clinically normal Miniature Schnauzers. Mean serum concentrations of 1,25-dihydroxyvitamin D in Miniature Schnauzers with calcium oxalate urolithiasis were similar to concentrations of clinically normal Miniature Schnauzers.     

Analysis of 2735 canine uroliths in Spain and Portugal. A retrospective study: 2004-2006

The objective of the study was to evaluate epidemiological data derived from 2735 canine uroliths received by Hill’s Pet Nutrition from Spain and Portugal between January 2004 and December 2006. The results of quantitative analysis from Minnesota Urolith Center (MUC) were compared with that from other countries and interrelations of mineral composition, age, breed, and gender were determined. The most frequent calculus was calcium oxalate (38.1%) followed by struvite (32.9%). Eighty-three breeds plus crossbreeds (25%) were identified. In all of them, but Dalmatians, calcium oxalate and struvite accounted for 71–78%. The mean age of urolith appearance was 7.6 years. There was a significant difference in the frequency of different uroliths composition among the six most common breeds presenting urolithiasis in Spain and Portugal (Yorkshire terrier, Miniature Schnauzer, Cocker Spaniel, Poodle, Shih Tzu and Dalmatian). This is the first report on xanthine urolithiasis found in Spain. Prevalence of cystine calculi was significantly lower (3.2%) than that reported previously in parts of Spain (26%).     

In vitro prediction of canine urolith mineral composition using computed tomographic mean beam attenuation measurements

Determination of urolith mineral composition is critical for management of urolithiasis in dogs and cats. Using computed tomography, urolith physical density, and hence chemical composition, can be quantified using mean beam attenuation measurements (Hounsfield units; HU). This study was designed to establish in vitro reference ranges for three types of compositionally pure uroliths retrieved from dogs. Sixty-six canine uroliths (22 uric acid, 21 calcium oxalate, 14 struvite, nine mixed or compound) were placed in a phantom array. Uroliths were scanned at 120 kVp, 200 mA, and 80 kVp, 200 mA. The region of interest (ROI) for mean HU calculation was determined using two techniques, and reference ranges were calculated for each kVp using either ROI technique. HU for urolith types of pure composition were statistically different (Wilcoxon's two-sample test, P < 0.0083 [Bonferonni correction with six comparisons for total P < 0.05]) using both ROI techniques at either kVp. Struvite uroliths were not statistically different from mixed or compound uroliths. The accuracy for determination of composition of pure uroliths ranged from 86% to 93%; the prediction accuracy for each urolith mineral type and for all uroliths in general was highest when the ROI was hand-drawn just within the visible urolith border at 80 kVp. Technique of ROI determination and kVp that yielded the highest sensitivity, specificity, and positive and negative predictive values varied for each urolith type. Therefore, in this study, HU could be used to differentiate three types of uroliths of pure mineral composition in vitro. Further studies are needed to determine the predictive value of HU in vivo.     

Etiopathogenesis of canine struvite urolithiasis

Urine must be oversaturated with magnesium ammonium phosphate for struvite uroliths to form. Oversaturation of urine with magnesium ammonium phosphate may be associated with several factors, including urinary tract infections with urease-producing microbes, alkaline urine, diet, and genetic predisposition. Of the urease-producing microbes, staphylococci are most struvitogenic in dogs. The precise mechanisms resulting in formation of sterile struvite uroliths in dogs have not been determined.     

Deafness prevalence and pigmentation and gender associations in dog breeds at risk

Hearing function was tested in dogs from breeds at risk for pigment-associated congenital sensorineural deafness - Dalmatian, English setter (ES), English cocker spaniel (ECS), bull terrier (BT), Australian cattle dog (ACD), whippet, Catahoula leopard dog, and Jack Russell terrier. Deafness prevalence was highest in Dalmatians and lowest in ECS. Phenotype correlation studies were performed in breeds with >100 brainstem auditory evoked responses (BAER) tested subjects. No gender differences were observed. No differences were seen between black- and liver-spotted Dalmatians, among the ES roan colour varieties, among the ECS parti varieties, or among the ACD colour varieties. Blue eyes were positively associated and patches were negatively associated with deafness in the Dalmatian. Blue eyes were also associated with deafness in the ES and ECS. White BT were more likely than coloured BT to be deaf. Having one or more parent's ear deaf was positively associated with deafness in Dalmatians, ES, and ECS.     

Etiopathogenesis, clinical manifestations, and management of canine calcium oxalate urolithiasis

Calcium oxalate uroliths are commonly called metabolic uroliths because they are sequelae of a variety of metabolic abnormalities that alter the composition of body fluids and urine. Factors incriminated in the etiopathogenesis of calcium oxalate urolithiasis include hypercalciuria, hyperoxaluria, and hyperuricosuria. The predominant type of calcium oxalate urolith encountered in dogs is the monohydrate form; however, the dihydrate form may also occur. Male dogs have been more frequently affected than female dogs. Medical therapy should be formulated with the goal of reducing urine concentration of calculogenic substances.     

Medical management of male and female cats with nonobstructive lower urinary tract disease

This case is typical of recurrent urolithiasis managed by repeated surgery. Retrospective assessment of the disorder indicates the need for quantitative analyses of uroliths removed by cystotomy. Compliance of the owners with recommendations to minimize recurrent urolithiasis might have been beneficial. Results of medical therapy designed to induce dissolution of uroliths in this case are representative of preliminary findings of medical dissolution of naturally occurring struvite uroliths in ten other cats. It is of interest that the uroliths dissolved even though no effort was made to induce diuresis. The underlying cause of UTI in this patient may have been damage to the lower urinary tract induced by previous diagnostic and therapeutic procedures and/or sterile struvite uroliths that compromised local host defense mechanisms. Lack of urease production by the uropathogens suggests that they did not play a causative role in formation of uroliths. The need for preventative therapy of recurrent formation of uroliths after their medical dissolution is worthy of further comment. In this patient, specific measures to prevent urolith recurrence were not initiated because it is a part of a prospective clinical study. In the event uroliths recur, medical therapy designed to induce dissolution of uroliths would be repeated. Need for long-term preventative therapy would be dependent on the time interval between recurrent episodes (weeks, months, or years), and the effectiveness of medical therapy for urolith dissolution. Long-term prophylactic therapy would include urine acidifiers and diets low in magnesium.     

Uric acid and phosphorus excretion in dogs with lymphosarcoma

Serum uric acid and phosphorus concentrations were determined for 27 dogs with multicentric lymphosarcoma before and after chemotherapy. Mean serum uric acid values in dogs before treatment were significantly higher (P less than 0.05) than those of a control group of healthy dogs. Serum uric acid values did not change after treatment. Of the 27 dogs, 13 had 24-hour urine collections to determine endogenous creatinine clearance and quantitation of uric acid and phosphorus excretion before and after treatment for lymphosarcoma. Mean values for 24-hour creatinine clearance before and after treatment were statistically similar in dogs with lymphosarcoma, although the values were lower than those in a normal range. Total urinary phosphorus excretions were increased significantly (P less than 0.01) after treatment without change in fractional excretion. Chemotherapeutic agents used accounted for the significant (P less than 0.05) increase in urine volume after treatment and may have affected the excretion of uric acid and phosphorus. Seemingly, dogs with uncomplicated lymphosarcoma rarely have renal dysfunction or clinically important alterations in uric acid or phosphorus excretion secondary to rapid tumor lysis. However, preexisting renal disease or systemic complications, such as hypercalcemia, may be associated with increased risk of further renal impairment during treatment.     

IN VITRO EVALUATION OF CONTRAST MEDIUM CONCENTRATION AND DEPTH EFFECTS ON THE RADIOGRAPHIC APPEARANCE OF SPECIFIC CANINE UROLITH MINERAL TYPES

Nine pure mineral types of canine uroliths (bladder or urethral origin only) identified in a chronologic sample from the Minnesota Urolith Center were compared to sequential dilutions of iodinated radiographic contrast medium in vitro. The uroliths studied were those composed of 100% magnesium ammonium phosphate, calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate appatite, calcium hydrogen phosphate dihydrate (brushite), ammonium acid urate, sodium acid urate, cystine, and silica. The radiopacity of the uroliths was classified as radiolucent, isopaque, or radiopaque, as compared to the radiopacity of the contrast medium solutions in which they were placed, using 2.0 mm and 5.0 mm depths in petri dishes radiographed using a table-top technique. A statistically significant relationship was found between the effective atomic number of the uroliths and the effective atomic number of the contrast medium solutions to which they were compared for the endpoints of isopacity, first luceney (in increasing iodine concentration sequence), and optimal visualization of internal architecture. In general, uroliths isopaque or radiolucent in contrast medium solutions weaker than 23.5 mgI₂/ml are most likely ammonium acid urate or sodium acid urate. Uroliths isopaque or radiolucent in contrast medium solutions between 23.5 mgI₂/ml and 44.4 mgI₂/ml are probably magnesium ammonium phosphate, cystine, or silica. Uroliths that remained radiopaque in solutions stronger than 44.4 mgI₂/ml, and particularly those radiopaque in contrast medium solutions stronger than 80 mgI₂/ml, almost always contained calcium. This relative opacity assessment is proposed for use in double contrast cystography as an aid in differentiating urolith mineral types clinically to facilitate appropriate use of medical protocols to dissolve uroliths or to prevent their growth or recurrence.     

Prevalence of canine uroliths. Minnesota Urolith Center

Uroliths obtained from 839 dogs were evaluated by quantitative methods. Struvite was the most prevalent mineral detected; newberyite, calcium oxalate, calcium phosphate, uric acid, sodium and ammonium urate, cystine, and silica were detected much less frequently. Seven per cent of the uroliths had an identifiable nucleus and one or more surrounding layers of different mineral types. Although uroliths were found in all parts of the urinary tract, the urinary bladder was most common. Uroliths of different composition were encountered in a variety of breeds of both sexes and different ages.     

Canine calcium phosphate uroliths

Uroliths composed primarily of calcium phosphate are identified in approximately 3 per cent of canine stone patients. Predisposing factors to the formation of calcium phosphate uroliths include elevated urine pH, hypercalciuria, and the presence of crystallization inhibitors and promoters. Medical therapy of patients forming calcium phosphate uroliths should initially be directed at removing factors contributing to urine supersaturation with calcium phosphate.     

Effects of urine pH modification on pharmacokinetics of phenobarbital in healthy dogs

Although pH modification is one of the effective strategies for dissolving or preventing uroliths, little is known about its effects on the pharmacokinetics of phenobarbital in dogs. Five spayed, female Beagles were fed with a twice‐daily diet that included potassium citrate and ammonium chloride for urine alkalinization and acidification, respectively. After a stabilizing period of 7 days, a single clinical dose of phenobarbital (3 mg/kg) was orally administered, and time‐course changes in its serum and urine concentrations were determined by high‐performance liquid chromatography. Total amounts of unchanged phenobarbital excreted into urine for 216 h were decreased by urine acidification and increased by urine alkalinization. The elimination half‐life of serum phenobarbital in dogs with urine alkalinization was shortened and Cl_R increased when compared with dogs with urine acidification. Other pharmacokinetic parameters, including C_max, T_max, AUC_0–216, Cl/F, and A_e0–216 were not changed by modification of the urine pH. These results suggest that the pH of urine is likely to be a determinant of the pharmacokinetics, especially urine excretion rate, of a clinical dose of oral phenobarbital. It is possible that the serum concentration of phenobarbital might be altered when a pH modifying‐diet is administered for the purpose of dissolving or preventing uroliths.     

Complex segregation analysis of deafness in Dalmatians

OBJECTIVE: To use pedigree analysis to evaluate the feasibility of a major locus model for deafness in Dalmatians. ANIMALS: 605 purebred Dalmatians from 42 families. PROCEDURE: Hearing loss was evaluated through the brainstem auditory-evoked response. Dogs were classified into mutually exclusive categories: normal hearing, unilaterally deaf, or bilaterally deaf. Information was collected on sex, coat color, presence or absence of a color patch at birth, and eye color. Statistical analyses were performed by use of regressive logistic models designed for complex segregation analysis. Genetic correlations among eye color, deafness, and color patch were estimated. RESULTS: Prevalence of hearing loss was 11% for dogs classified as unilaterally deaf and 5% for dogs that were bilaterally deaf. Complex segregation analysis detected statistical evidence of a single allele with an expected frequency of 0.21 that had an effect on the prevalence of deafness. Results of analyses suggested that this locus cannot completely explain the inheritance and incidence of deafness in Dalmatians. Genetic correlation estimates among deafness, eye color, and color patch revealed strong interrelationships among these characteristics. CONCLUSIONS AND CLINICAL RELEVANCE: To reduce the incidence of hearing loss in Dalmatians, unilaterally deaf, blue-eyed dogs should not be considered as potential parents.