Associations between dry dietary factors and canine calcium oxalate uroliths

OBJECTIVE: To identify factors in dry diets associated with the occurrence of calcium oxalate (CaOx) uroliths in dogs. ANIMALS: 600 dogs with CaOx uroliths and 898 dogs without urinary tract diseases. PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: Compared with diets with the highest concentrations of sodium, dry diets with the lowest concentrations of sodium, phosphorus, calcium, chloride, protein, magnesium, or potassium were linearly associated with increased risk of CaOx urolith formation. Significant nonlinear associations between increased occurrence of CaOx uroliths and urine acidifying potential and low moisture content were observed. Significant nonlinear associations between decreased occurrence of CaOx uroliths and carbohydrate and fiber contents were observed. A significant association between the occurrence of CaOx uroliths and dietary fat was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dry diets formulated to contain high concentrations of protein, calcium, phosphorus, magnesium, sodium, potassium, and chloride may minimize formation of CaOx uroliths. In addition, comparison of risk and protective factors of various diet ingredients fed to dogs with CaOx uroliths suggests that although similar findings were observed in canned and dry formulations, in general, greater risk is associated with dry formulations. However, before these hypotheses about dietary modifications are adopted by food manufacturers, they must be investigated by use of appropriately designed clinical studies of dogs with CaOx urolithiasis.     

Associations between dietary factors in canned food and formation of calcium oxalate uroliths in dogs

OBJECTIVE: To identify dietary factors in commercially available canned foods associated with the development of calcium oxalate (CaOx) uroliths in dogs. ANIMALS: 117 dogs with CaOx uroliths and 174 dogs without urinary tract disease. PROCEDURE: Case dogs were those that developed CaOx uroliths submitted to the Minnesota Urolith Center for quantitative analysis between 1990 and 1992 while fed a commercially available canned diet. Control dogs were those without urinary tract disease evaluated at the same veterinary hospital just prior to or immediately after each case dog. A content-validated multiple-choice questionnaire was mailed to each owner of case and control dogs with the permission of the primary care veterinarian. Univariate and multivariate logistic regressions for each dietary component were performed to test the hypothesis that a given factor was associated with CaOx urolith formation. RESULTS: Canned foods with the highest amount of protein, fat, calcium, phosphorus, magnesium, sodium, potassium, chloride, or moisture were associated with a decreased risk of CaOx urolith formation, compared with diets with the lowest amounts. In contrast, canned diets with the highest amount of carbohydrate were associated with an increased risk of CaOx urolith formation. CONCLUSIONS AND CLINICAL RELEVANCE: Feeding canned diets formulated to contain high amounts of protein, fat, calcium, phosphorus, magnesium, sodium, potassium, chloride, and moisture and a low amount of carbohydrate may minimize the risk of CaOx urolith formation in dogs.     

Effects of diet on urine composition of cats with calcium oxalate urolithiasis

Ten client-owned cats with calcium oxalate (CaOx) urolithiasis were evaluated to determine the effect of diet on urine CaOx saturation. Two dietary treatments were evaluated in each cat: the diet consumed just prior to urolith detection and a canned diet formulated to prevent CaOx uroliths. This study revealed that hypercalciuria is a consistent abnormality in cats with CaOx urolith formation. When urolith-forming cats consumed a diet formulated to prevent urolith formation, activity product ratios for CaOx (which estimate the degree to which urine is saturated with CaOx) were significantly lower. These results suggest that consumption of an appropriately formulated urolith-prevention diet will reduce recurrence of CaOx urolithiasis.     

The effect of urine acidification on calcium oxalate relative supersaturation in cats

There is an apparent reciprocal relationship between magnesium ammonium phosphate (MAP, struvite) and calcium oxalate (CaOx) urolithiasis incidence rate in cats. The number of struvite uroliths submitted for analysis over the past 35 years has been decreasing, with an increase in CaOx urolith submissions. Commercial diets aimed to dissolve struvite uroliths are typically acidified, and it has been suggested that dietary acidification increases urinary calcium excretion and the risk of CaOx crystallization. The objective of this study was to assess the effect of urine acidification on the relative supersaturation (RSS) of CaOx in cats, as a representation of crystallization risk. Four diets were extruded to contain identical nutrient contents, but with gradual acidification (0, 0.6, 1.3 and 1.9% sodium bisulphate substituted sodium chloride in diets A, B, C and D respectively). Thirteen adult cats were fed each diet sequentially for a minimum of 10 days. Average urine pH was 6.4, 6.2, 6.0 and 5.9 on diets A, B, C and D respectively (p < 0.0001). Struvite RSS decreased on diets inducing more acidic urine pH (p < 0.0001). Urinary calcium excretion and concentration increased with diets inducing lower urine pH (p < 0.0001), but oxalate excretion and concentration decreased (p < 0.001). CaOx RSS was not different between diets (p = 0.63). These results suggest that a lower diet base excess and resulting urine pH to support struvite dissolution do not increase the risk for CaOx crystallization in the range of urine pH representative of most commercial feline diets. Long-term studies are needed to confirm this.     

Association between patient-related factors and risk of calcium oxalate and magnesium ammonium phosphate urolithiasis in cats

OBJECTIVE: To determine whether breed, age, sex, or reproductive status (i.e., neutered versus sexually intact) was associated with the apparent increase in prevalence of calcium oxalate (CaOx) uroliths and the decrease in prevalence of magnesium ammonium phosphate (MAP) uroliths in cats over time. DESIGN: Case-control study. ANIMALS: Case cats consisted of cats with CaOx (n = 7,895) or MAP (7,334) uroliths evaluated at the Minnesota Urolith Center between 1981 and 1997. Control cats consisted of cats without urinary tract disease admitted to veterinary teaching hospitals in the United States and Canada during the same period (150,482). PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: British Shorthair, Exotic Shorthair, Foreign Shorthair, Havana Brown, Himalayan, Persian, Ragdoll, and Scottish Fold cats had an increased risk of developing CaOx uroliths, as did male cats and neutered cats. Chartreux, domestic shorthair, Foreign Shorthair, Himalayan, Oriental Shorthair, and Ragdoll cats had an increased risk of developing MAP uroliths, as did female cats and neutered cats. Cats with CaOx uroliths were significantly older than cats with MAP uroliths. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that changes in breed, age, sex, or reproductive status did not contribute to the apparent reciprocal relationship between prevalences of CaOx and MAP uroliths in cats during a 17-year period. However, cats of particular breeds, ages, sex, and reproductive status had an increased risk of developing CaOx and MAP uroliths.     

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

Prednisolone (10 mg PO q24h) 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 prednisolone, 24-hour urine pH was lower and 24-hour urine excretion of creatinine, magnesium, phosphate, and potassium was higher than when cats received placebo. No significant difference was found in urinary relative supersaturation for calcium oxalate (CaOx) or struvite between treatment groups. Prednisolone administration did not induce diuresis, nor was it associated with increased calcium excretion or urinary saturation for CaOx in these healthy cats. Results of this study, however, should not be extrapolated to cats that form CaOx uroliths associated with idiopathic hypercalcemia.     

Nutrient intake and urine composition in calcium oxalate stone-forming dogs: comparison with healthy dogs and impact of dietary modification

Nutrient intake and urine composition were analyzed in calcium oxalate (CaOx)stone-forming and healthy control dogs to identify factors that contribute to CaOx urolithiasis. Stone-forming dogs had significantly lower intake of sodium, calcium, potassium, and phosphorus and significantly higher urinary calcium and oxalate concentrations, calcium excretion, and CaOx relative supersaturation (RSS). Feeding a diet used in the treatment of canine lower urinary tract disease for 1 month was associated with increased intake of moisture, sodium, and fat; reduced intake of potassium and calcium; and decreased urinary calcium and oxalate concentrations, calcium excretion, and CaOx RSS. No clinical signs of disease recurrence were observed in the stone-forming dogs when the diet was fed for an additional 11 months. The results suggest that hypercalciuria and hyperoxaluria contribute to the formation of CaOx uroliths in dogs and show that dietary modifications can alter this process.     

Evaluation of effects of dietary carbohydrate on formation of struvite crystals in urine and macromineral balance in clinically normal cats

OBJECTIVE: To evaluate effects of dietary carbohydrate on urine volume; struvite crystal formation; and calcium, phosphorus, and magnesium balance in clinically normal cats. ANIMALS: 21 healthy adult cats (15 sexually intact males and 6 sexually intact females). PROCEDURE: Diets containing no carbohydrate source (control diet), control plus starch, or control plus fiber were given in a 3 X 3 Latin-square design. The diets were available ad libitum in study 1 (n = 12) and given under restrictions in study 2 (9) to equalize daily intakes of crude protein among the 3 groups. Formation of struvite crystals and balance of calcium, phosphorus, and magnesium were measured. RESULTS: Urine volume was lower in the starch group and fiber group in study 1, whereas no differences were detected among the groups in study 2. Urinary pH and struvite activity product were higher in the starch group in both studies, and the fiber group also had higher struvite activity product in study 2. In both studies, urinary concentrations of HCl-insoluble sediment were higher in the starch group and fiber group. In the fiber group, a net loss of body calcium, phosphorus, and magnesium was detected in study 2. CONCLUSIONS AND CLINICAL RELEVANCE: Starch and fiber in diets potentially stimulate formation of struvite crystals. Hence, reducing dietary carbohydrate is desirable to prevent struvite urolith formation. In addition, a net loss of body calcium, phosphorus, and magnesium during feeding of the fiber diet suggests that dietary inclusion of insoluble fiber could increase macromineral requirements of cats.     

Impact of hyperlipidaemia on intermediary metabolism,faecal microbial metabolites and urinary characteristics of lipoprotein lipase deficient vs. normal cats

Findings in humans and rats indicate that hyperlipidaemia may be associated with enhanced endogenous oxalate (Ox) synthesis, which may be relevant for calcium oxalate (CaOx) urolith formation. Moreover, changes in lipid metabolism are proposed to negatively affect gut microbiota. This study aimed to investigate those potential interactions in hyperlipidaemic cats. Therefore, 10 normal control cats and seven lipoprotein lipase (LPL)‐deficient cats were fed a low‐fat diet for seven weeks. During the last week of the study, cats were housed in metabolic cages to collect urine and faeces. Blood was taken on the last day of the study. The LPL‐deficient cats had significantly higher serum triglyceride concentrations than normal cats, while lactate dehydrogenase (LDH) activity was not different. Urinary relative supersaturation with CaOx, urinary Ox, calcium, and citrate excretions, and urine pH did not differ between groups. Lower faecal acetic, propionic and total short‐chain fatty acid concentrations were observed in the LPL‐deficient cats. In conclusion, hyperlipidaemia does not appear to be a specific risk factor for CaOx urolith formation in cats. In contrast to results in rats, hyperlipidaemia was not accompanied by elevated serum LDH activity. As LDH can synthesise Ox from glycolate or other precursors, this might be one possible explanation for the similar urinary parameters in the LPL‐deficient and normal cats. Non‐diet‐induced hyperlipidaemia was not associated with marked changes in faecal microbial metabolites, suggesting no differences in the composition of the intestinal microbiota.     

Evaluation of trends in urolith composition in cats: 5,230 cases (1985-2004)

OBJECTIVE: To determine trends in urolith composition in cats. DESIGN: Retrospective case series. SAMPLE POPULATION: 5,230 uroliths. PROCEDURES: The laboratory database for the Gerald V. Ling Urinary Stone Analysis Laboratory was searched for all urolith submissions from cats from 1985 through 2004. Submission forms were reviewed, and each cat's age, sex, breed, and stone location were recorded. RESULTS: Minerals identified included struvite, calcium oxalate, urates, dried solidified blood, apatite, brushite, cystine, silica, potassium magnesium pyrophosphate, xanthine, and newberyite. During the past 20 years, the ratio of calcium oxalate stones to struvite stones increased significantly. When only the last 3 years of the study period were included, the percentage of struvite stones (44%) was higher than the percentage of calcium oxa-late stones (40%). The most common location for both types of uroliths was the bladder. The number of calcium oxalate-containing calculi in the upper portion of the urinary tract increased significantly during the study period. The number of apatite uroliths declined significantly and that of dried solidified blood stones increased significantly, compared with all other stone types. No significant difference in the number of urate stones was detected. CONCLUSIONS AND CLINICAL RELEVANCE: The increasing proportion of calcium oxalate uroliths was in accordance with findings from other studies and could be a result of alterations in cats' diets. However, the decreased percentage of calcium oxalate calculi and increased percentage of struvite calculi observed in the last 3 years may portend a change in the frequency of this type of urolith.     

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.     

Patient and environmental factors associated with calcium oxalate urolithiasis in dogs

OBJECTIVE: To test the hypothesis that breed, age, sex, body condition, and environment are risk factors for development of calcium oxalate uroliths in dogs. DESIGN: Case-control study. ANIMALS: 1,074 dogs that formed calcium oxalate uroliths and 1,724 control dogs that did not have uroliths. PROCEDURE: A validated multiple-choice questionnaire was designed to collect information from veterinarians and owners within 1 year of the date of urolith detection concerning signalment and environment of the dogs. Univariate and multivariate analyses were performed to calculate odds ratios to assess whether breed, age, sex, body condition, and environment were risk factors for calcium oxalate urolith formation. RESULTS: Middle-aged (8- to 12-year-old) castrated male dogs had increased risk for formation of calcium oxalate uroliths. Urolith formation was also associated with increasing age. Dogs of certain breeds, including Miniature and Standard Schnauzer, Lhasa Apso, Yorkshire Terrier, Bichon Frise, Shih Tzu, and Miniature and Toy Poodle, had increased risk for developing calcium oxalate uroliths. Overweight dogs also had increased risk. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of patient and environmental risk factors for development of calcium oxalate uroliths may facilitate development of surveillance strategies that result in earlier detection of this disease. Modification of environmental factors and body weight may minimize calcium oxalate urolith formation and recurrence.     

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.     

Calcium oxalate stones in feline littermates.

Two feline littermates were diagnosed with calcium oxalate uroliths. Both had been maintained on a commercially available dry diet with reduced magnesium and urine acidifying properties. One female littermate was diagnosed by visualising the stones by radiographs while the second littermate, also female, became blocked when one of the uroliths lodged in the urethra. Two other, unrelated cats in the household, of similar age and raised under the same conditions, did not develop calcium oxalate uroliths.     

Characterization of the urogenital microbiome in Miniature Schnauzers with and without calcium oxalate urolithiasis

BackgroundCalcium oxalate (CaOx) uroliths are common in dogs. Humans with CaOx urolithiasis exhibit alterations of the urinary and urogenital microbiomes that might mediate urolith formation. Detection of urogenital microbes associated with CaOx in dogs could inform disease pathophysiology.ObjectiveTo identify compositional differences in the urogenital microbiome of Miniature Schnauzers with and without CaOx uroliths.AnimalsNineteen midstream, voided urine samples from Miniature Schnauzers with (n = 9) and without (n = 10) a history of CaOx urolithiasis.MethodsAnalytical cross‐sectional study. Microbial DNA was extracted from previously frozen urine samples and sequenced for the bacterial 16S rRNA V3‐V4 hypervariable regions. Diversity and composition of microbial populations were compared between urolith formers and controls.ResultsAlpha and beta diversity measures were similar between groups. Five individual bacterial taxa differed in abundance (indicator values >0.5 and P < .05): Acinetobacter, 2 Geobacillus variants, and Hydrogenophaga were overrepresented in the urine of urolith formers, and Sphingopyxis was overrepresented in controls. Two distinct subtypes of urine microbial composition were observed based on beta diversity measures, independent of urolith status, and other clinical variables.Conclusions and Clinical ImportanceAlthough we did not detect a difference in the overall urogenital microbial composition between groups, observed differences in individual bacterial taxa might be clinically relevant. For example, Acinetobacter was overrepresented in urolith formers and is associated with CaOx urolithiasis in humans. Two unique clusters of the microbiome were identified, independent of urolith status, which may represent distinct urotypes present in Miniature Schnauzers.     

Medical dissolution of feline struvite urocystoliths

The efficacy of a diet designed to facilitate dissolution of feline magnesium ammonium phosphate (struvite) uroliths was evaluated in 30 cases of urolithiasis, sterile struvite uroliths dissolved in a mean of 36 days after initiation of dietary treatment. In 5 cases of urolithiasis, struvite urocystoliths associated with urease-negative bacterial urinary tract infection dissolved in a mean of 23 days after initiation of dietary and antimicrobial treatment. In 3 cases of urolithiasis, struvite urocystoliths associated with urease-positive staphylococcal urinary tract infection dissolved in a mean of 79 days after initiation of dietary and antimicrobial treatment. Dissolution of uroliths in cats fed the treatment diet was associated with concomitant remission of dysuria, hematuria, and pyuria, and reduction in urine pH and struvite crystalluria. In one case, a urocystolith composed of 100% ammonium urate, and in another case, a urolith composed of 60% calcium phosphate, 20% calcium oxalate, and 20% magnesium ammonium phosphate did not dissolve.     

Evaluation of 21 426 feline bladder urolith submissions to the Canadian Veterinary Urolith Centre (1998–2014)

This study reports emerging trends in feline urolithiasis in Canada during the past 16.8 y, evaluates associations of breed and gender with urolith types, and reports on feline submissions from outside of Canada. Struvite and calcium oxalate uroliths comprised > 90% of all uroliths submitted. In cats, oxalate submissions outnumbered struvite submissions from Canada, Hong Kong, Denmark, and the United Arab Emirates, while Australian struvite submissions outnumbered calcium oxalate submissions. In Canada, the majority of urolith submissions were from domestic cats followed by Himalayan, Persian, and Siamese cats. Males were more likely to form calcium oxalate uroliths and females were more likely to develop struvite uroliths. Compared to domestic short-haired cats, Tonkinese, Burmese, Devon rex, Himalayan, Persian, and Siamese cats were significantly associated with calcium oxalate urolith submission. Egyptian mau, Birman, ocicat, and Siamese breeds were over-represented amongst urate submissions.     

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.     

Idiopathic hypercalcemia in cats

Unexplained hypercalcemia has been increasingly recognized in cats since 1990. In some instances, hypercalcemia has been associated with calcium oxalate urolithiasis, and some affected cats have been fed acidifying diets. We studied the laboratory findings, clinical course, and treatment of 20 cats with idiopathic hypercalcemia. Eight (40%) of the cats were longhaired and all 14 cats for which adequate dietary history was available had been fed acidifying diets. Clinical signs included vomiting (6 cats), weight loss (4 cats), dysuria (4 cats), anorexia (3 cats), and inappropriate urinations (3 cats). Hypercalcemia was mild to moderate in severity. and serum parathyroid hormone concentrations were normal or low. Serum concentrations of phosphorus, parathyroid hormone-related peptide, 25-hydroxycholecalciferol, and calcitriol were within the reference range in most cats. Diseases commonly associated with hypercalcemia (eg, neoplasia, primary hyperparathyroidism) were not identified despite thorough medical evaluations and long-term clinical follow-up. Azotemia either did not develop (10 cats) or developed after the onset of hypercalcemia (3 cats), suggesting that renal failure was not the cause of hypercalcemia in affected cats. Seven of 20 cats (35%) had urolithiasis, and in 2 cats uroliths were composed of calcium oxalate. Subtotal parathyroidectomy in 2 cats and dietary modification in 11 cats did not result in resolution of hypercalcemia. Treatment with prednisone resulted in complete resolution of hypercalcemia in 4 cats.     

Update: Management of calcium oxalate uroliths in dogs and cats.

Calcium oxalate has become the most common mineral occurring in canine and feline uroliths. Although calcium oxalate urolith formation may be a consequence of metabolic disease, the underlying cause is not identified in many dogs and cats. Currently, there is no successful medical dissolution protocol, and calcium oxalate uroliths must be removed physically if causing problems. Effective preventative protocols are available for dogs and cats, although they are not uniformly successful.