Association between dietary factors and calcium oxalate and magnesium ammonium phosphate urolithiasis in cats.

OBJECTIVE: To identify dietary factors associated with the increase in occurrence of calcium oxalate (CaOx) uroliths and the decrease in occurrence of magnesium ammonium phosphate (MAP) uroliths in cats. DESIGN: Case-control study. ANIMALS: 173 cats with CaOx uroliths, 290 cats with MAP uroliths, and 827 cats without any urinary tract diseases. PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: Cats fed diets low in sodium or potassium or formulated to maximize urine acidity had an increased risk of developing CaOx uroliths but a decreased risk of developing MAP uroliths. Additionally, compared with the lowest contents, diets with the highest moisture or protein contents and with moderate magnesium, phosphorus, or calcium contents were associated with decreased risk of CaOx urolith formation. In contrast, diets with moderate fat or carbohydrate contents were associated with increased risk of CaOx urolith formation. Diets with the highest magnesium, phosphorus, calcium, chloride, or fiber contents and moderate protein content were associated with increased risk of MAP urolith formation. On the other hand, diets with the highest fat content were associated with decreased risk of MAP urolith formation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that diets formulated to contain higher protein, sodium, potassium, moisture, calcium, phosphorus, and magnesium contents and with decreased urine acidifying potential may minimize formation of CaOx uroliths in cats. Diets formulated to contain higher fat content and lower protein and potassium contents and with increased urine acidifying potential may minimize formation of MAP uroliths.

Evaluation of urinary carnitine and taurine excretion in 5 cystinuric dogs with carnitine and taurine deficiency.

Five client owned dogs with cystinuria were diagnosed with carnitine and taurine deficiency while participating in a clinical trial that used dietary management of their urolithiasis. Stored 24-hour urine samples collected from the cystinuric dogs before enrollment in the clinical diet trial were quantitatively evaluated for carnitine and taurine. These results were compared to those obtained from 18 healthy Beagles. Both groups of dogs were fed the same maintenance diet for a minimum of 2 weeks before 24-hour urine collection. The protocol used for 24-hour urine collections was the same for cystinuric dogs and healthy Beagles except that cystinuric dogs were catheterized at baseline, 8 hours, 12 hours, and at the end of the collection, whereas Beagles were catheterized at baseline, 8 hours, and at the end of the collection. Three of 5 dogs with cystinuria had increased renal excretion of carnitine. None of the cystinuric dogs had increased renal excretion of taurine, but cystinuric dogs excreted significantly less (P < .05) taurine in their urine than the healthy Beagles. Carnitinuria has not been recognized previously in either humans or dogs with cystinuria, and it may be 1 risk factor for developing carnitine deficiency. Cystinuric dogs in this study were not taurinuric; however, cystine is a precursor amino acid for taurine synthesis. Therefore, cystinuria may be 1 risk factor for developing taurine deficiency in dogs. We suggest that dogs with cystinuria be monitored for carnitine and taurine deficiency or supplemented with carnitine and taurine.

Effects of dietary fat and carnitine on urine carnitine excretion in healthy dogs.

Turnover of carnitine in the body is primarily the result of renal excretion, and high-fat (HF) diets have been shown to increase urine carnitine excretion in healthy people. Recently, increased renal excretion of carnitine was observed in dogs diagnosed with cystinuria and carnitine deficiency. Carnitine deficiency has been linked to dilated cardiomyopathy and lipid storage myopathies in dogs and humans, and low-fat (LF) diets have been beneficial in some human patients with carnitine deficiency. In addition, HF, protein-restricted diets are often recommended for management of cystinuria in dogs. However, whether HF diets increase renal carnitine excretion in dogs or whether dogs with carnitine deficiency would benefit from LF diets remains unknown. Therefore, the purpose of this study was to determine the influence of dietary fat and carnitine on renal carnitine excretion in healthy dogs. Results from this study revealed that an HF diet increased urine carnitine excretion in dogs; however, carnitine excretion with the HF diet was not significantly different from that in dogs consuming an LF diet. Nonetheless, these results raise the possibility that increased renal carnitine excretion associated with HF diets could be one risk factor for development of carnitine deficiency in dogs with an underlying disorder in carnitine metabolism, and some dogs with carnitine deficiency may benefit from an LF diet. Another important observation in this study was that renal excretion of carnitine exceeded dietary intake in all diet groups, confirming previous reports that concluded that canine renal tubular cells reabsorb carnitine poorly when compared with those of humans.

Calcium oxalate crystalluria in a goat.

As part of a routine health evaluation of an 8-month-old female Nubian goat, serum biochemical analyses and urinalysis were performed. Most serum biochemical values including concentrations of blood calcium and indicators of urinary system dysfunction, such as blood urea nitrogen, creatinine, and phosphorous concentrations, were within reference ranges. An aliquot of voided urine was hypersthenuric and acidic and contained numerous typical cuboidal-bipyramidal calcium oxalate dihydrate crystals and unique rectangular parallelepiped crystals that were confirmed by energy dispersive X-ray microanalysis as being of calcium oxalate dihydrate composition. We hypothesize that the calcium oxalate crystals resulted from a diet containing calcium and oxalic acid. Treatment was not administered, and the goat remained healthy during the ensuing year.

Analysis of 77,000 canine uroliths. Perspectives from the Minnesota Urolith Center.

Of the hundreds of minerals that are found in the earth, most canine uroliths are comprised of only six types: (1) magnesium ammonium phosphate, (2) calcium oxalate, (3) calcium phosphates, (4) ammonium urate and other salts or uric acid, (5) cystine, or (6) silica. Each type has characteristics that allow its identification. During the past two decades, the prevalence of calcium oxalate canine uroliths has dramatically increased, while struvite has decreased. The most effective treatment and prevention protocols are based on knowledge of the primary mineral type comprising the urolith.

Medical dissolution and prevention of canine struvite urolithiasis. Twenty years of experience.

Two types of canine struvite uroliths have been recognized: infection-induced struvite is the most common type; sterile struvite is uncommonly recognized. Infection-induced struvite is most commonly associated with urease-producing staphylococcal UTI. For dogs that qualify, medical dissolution is an effective method of treatment. Medical dissolution protocols encompass: (1) eradication or control of UTI; (2) use of calculolytic diets; and (3) administration of urease inhibitors to patients with persistent UTI caused by urease-producing microbes.

Epidemiology of canine calcium oxalate uroliths. Identifying risk factors.

Calcium oxalate uroliths are most commonly encountered in Miniature Schnauzers, Lhaso Apsos, Yorkshire Terriers, Bichons Frises, Shih Tzus, and Miniature Poodles. They are more common in males than females, and more common in older than young dogs. Dogs that form abnormal nephrocalcin are also predisposed to calcium oxalate uroliths. Dietary risk factors for calcium oxalate uroliths include excessive calcium supplementation or excessive calcium restriction, excessive oxalic acid, high protein, high sodium, restricted phosphorus, restricted potassium, and restricted moisture (dry formulations). Dogs with hyperadrenocorticism or hypercalcemia are predisposed to calcium oxalate urolith formation.

Canine urate urolithiasis. Etiopathogenesis, diagnosis, and management.

Etiopathologic factors predisposing to urate lithogenesis in Dalmatian and non-Dalmatian dogs represent diverse pathologic and/or physiologic processes involving purine nucleotide and ammonia synthesis, biodegradation, and excretion. Predisposing factors for urate urolith formation include hyperuricemia, hyperammonemia, hyperuricosuria, hyperammonuria, aciduria, and genetic predisposition. Medical therapy of dogs forming urate uroliths should be directed at modifying these predisposing factors through dietary modification, administration of allopurinol, and/or surgical correction of portovascular anomalies if present. The precise mechanisms resulting in urate urolith formation in dogs have not been determined.

Canine cystine urolithiasis. Cause, detection, treatment, and prevention.

Cystine uroliths are a sequela to cystinuria, an inherited renal tubular defect in reabsorption of cystine and some other amino acids. At the Minnesota Urolith Center, 67 breeds of dogs were identified, including English Bulldogs, Dachshunds, Mastiffs, and Newfoundlands. In some dogs, the severity of cystinuria may decline with advancing age. Current recommendations for dissolution of cystine uroliths include various combinations of diet modification, diuresis administration of 2-MPG, and alkalinization of urine.

Canine silica urolithiasis. Risk factors, detection, treatment, and prevention.

Uroliths containing 70% or greater silica comprise approximately 1% of the canine uroliths submitted to the Minnesota Urolith Center. Male dogs are far more commonly affected than females. In our series, 84 different breeds were affected. Currently available data suggest dietary factors play a role in their formation. Diagnosis is facilitated by the characteristic jackstone configuration of silica uroliths, but must be confirmed by quantitative analysis. Voiding urohydropropulsion or surgery are currently the most practical methods of removal of silica uroliths.

Canine and feline nephrolithiasis. Epidemiology, detection, and management.

Calcium oxalate (39%) and struvite (33%) were the predominant mineral types in canine nephroliths submitted to the Minnesota Urolith Center. Urate salts (12%) and calcium phosphate (2%) occurred less frequently. Provided they are not causing obstruction, struvite nephroliths may be dissolved with medical protocols. Although there are no dissolution protocols for nephroliths containing calcium, risk-benefit ratios should be considered before proceeding with surgery.

Drug-induced urolithiasis.

Diagnostic and therapeutic drugs may enhance urolithiasis in one or a combination of ways, including: (1) alteration of urine pH in such fashion as to create an environment that increases the solubility of some lithogenic substances, (2) alteration of glomerular filtration rate, tubular reabsorption, and tubular secretion of drugs of endogenous substances so as to enhance promoters or impair inhibitors of urolithiasis, and (3) precipitation (e.g., drugs or their metabolites) to form a portion or all of a urolith.

Voiding urohydropropulsion. Lessons from 5 years of experience.

Voiding urohydropropulsion is a nonsurgical method of removing uroliths from the urinary bladder. Any urocystolith of sufficient size to pass through the distended urethral lumen can be safely and effectively removed by this technique. Compared to cystotomy, voiding urohydropropulsion offers several advantages: urolith removal can be performed in minutes, anesthetic period is shorter, postprocedural dysuria and hematuria are less severe, and it provides greater success for complete removal of small urocystoliths. This technique is not suitable for removal of large urocystoliths or uroliths that become lodged in the urethral lumen.

Bioavailability and pharmacokinetics of intravenously and orally administered allopurinol in healthy beagles.

OBJECTIVES: To determine bioavailability and pharmacokinetic parameters for allopurinol and its active metabolite, oxypurinol. ANIMALS: 6 healthy, reproductively intact female Beagles, 4.9 to 5.2 years old, and weighing 9.5 to 11.5 kg. PROCEDURE: In the first part of the study, allopurinol was administered IV at a dosage of 10 mg/kg of body weight to 3 dogs and 5 mg/kg to 3 dogs; the sequence was then reversed. In the second part of the study, allopurinol was administered orally at a dosage of 15 mg/kg to 3 dogs and 7.5 mg/kg to 3 dogs; the sequence was then reversed. In the third part of the study, allopurinol was administered IV (10 mg/kg), orally (15 mg/kg) with food, and orally (15 mg/kg) without food. Plasma samples were obtained at timed intervals, and concentrations of allopurinol and oxypurinol were determined. RESULTS: Maximal plasma allopurinol concentration and area under plasma allopurinol and oxypurinol concentration-time curves were 2 times greater when dogs were given 10 mg of allopurinol/kg IV, compared with 5 mg/kg, and when dogs were given 15 mg of allopurinol/kg orally, compared with 7.5 mg/kg. Allopurinol elimination half-life, time to reach maximal plasma oxypurinol concentration, and oxypurinol elimination half-life were significantly greater when dogs received 10 mg of allopurinol/kg IV, compared with 5 mg/kg, and when dogs received 15 mg of allopurinol/kg orally, compared with 7.5 mg/kg. CONCLUSIONS: Elimination of allopurinol is dependent on nonlinear enzyme kinetics. The bioavailability of allopurinol, and pharmacokinetic parameters of allopurinol and oxypurinol after oral administration of allopurinol, are not affected by administration with food. CLINICAL RELEVANCE: A dose threshold exists beyond which additional allopurinol would not substantially further inhibit xanthine oxidase activity. Oral administration of > 15 mg of allopurinol/kg to dogs would not be expected to result in greater reduction of plasma and urine uric acid concentrations. Also, allopurinol may be administered to dogs for dissolution or prevention of urate uroliths without regard to time of feeding.

Influence of two diets on pharmacokinetic parameters of allopurinol and oxypurinol in healthy beagles.

OBJECTIVES: To determine whether diet influences the metabolism of IV administered allopurinol in healthy dogs. ANIMALS: 6 healthy female Beagles, 4.9 to 5.2 years old and weighing 9.6 to 11.5 kg. PROCEDURES: Allopurinol was administered IV (10 mg/kg) while dogs consumed a 10.4% protein (dry weight), casein-based diet or a 31.4% (dry weight), meat-based diet. After each dose, plasma samples were obtained at timed intervals, and concentrations of allopurinol and its active metabolite, oxypurinol, were determined by high-performance liquid chromatography. An iterative, nonlinear regression analytical program was used to determine the weighted least-squares, best-fit curves for plasma allopurinol and oxypurinol concentration-time data. From these data, pharmacokinetic parameters were calculated. RESULTS: Pharmacokinetic parameters for allopurinol and oxypurinol were not different when comparing the effect of diet. CONCLUSION: There is no influence of diet on pharmacokinetic parameters of allopurinol or oxypurinol. CLINICAL RELEVANCE: In contrast to observations in human beings, allopurinol metabolism is not influenced by diet. Therefore, formation of xanthine-containing calculi in dogs consuming a high-protein diet and receiving allopurinol is probably not attributable to alteration of allopurinol metabolism.

Effects of time and dilution on concentration of xanthine in frozen urine and plasma of dogs.

OBJECTIVE: To evaluate the effects of dilution on stability of xanthine in canine urine stored at -20 C, and to evaluate the effects of storage at -20 C on stability of xanthine in canine plasma. ANIMALS: 6 reproductively intact female Beagles, 3.9 to 4.2 years old and weighing 8.5 to 10.1 kg. PROCEDURE: Dogs were fed a 31.4% protein (dry weight), meat-based diet for 21 days, and administered allopurinol (15 mg/kg of body weight, q 12 h) during days 14 to 21; urine and plasma samples were obtained on day 22. Urine samples were preserved undiluted or diluted, and divided into 1-ml aliquots for storage at -20 C for 1 to 12 weeks. Plasma samples were divided into 1-ml aliquots for storage at -20 C for 1 to 12 weeks. Urine and plasma xanthine concentrations were measured on day of collection (baseline) and after 1, 2, 4, 6, 9, and 12 weeks. RESULTS: Dilution of urine samples did not have a significant effect on consistency of xanthine concentration measured for up to 12 weeks of storage. Although xanthine concentration did not differ significantly between undiluted and diluted urine samples, average xanthine concentration measured in diluted samples was consistently higher, compared with that in undiluted samples. Compared with baseline values, plasma xanthine concentration was significantly lower at 6, 9, and 12 weeks of storage. CONCLUSIONS: Measurement of xanthine concentration is reproducible in undiluted or diluted urine samples for up to 12 weeks, although dilution may provide better results. Measurement of plasma xanthine concentration is reproducible in samples stored for up to 4 weeks. CLINICAL RELEVANCE: To ensure reproducibility of measurements of xanthine concentration in urine samples collected from dogs that are affected with urate uroliths and receiving allopurinol, urine should be diluted 1:20 with deionized water. These measurements may be useful for monitoring dogs that are receiving allopurinol for dissolution or prevention of urate uroliths.

Feline perineal urethrostomy: a potential cause of feline lower urinary tract disease.

Perineal urethrostomies are associated with complications that may mimic primary causes of feline lower urinary tract disorders. Though postoperative urethral strictures may be minimized by proficiency with an effective surgical technique, removal of the distal urethra may result in bacterial urinary tract infections in 25% to 30% of patients after surgery. Urinary tract infections caused by urease-producing microbes may induce struvite urolith formation. Thus the prophylactic benefits of minimizing recurrent urethral obstruction by urethrostomy must be weighed against a long-term predisposition to recurrent bacterial urinary tract infection and urolith formation.

Prednisolone therapy of idiopathic feline lower urinary tract disease: a double-blind clinical study.

A double-blind clinical study was performed to evaluate prednisolone as treatment for idiopathic feline lower urinary tract disease. No differences in response were observed in prednisolone- and placebo-treated cats.

Diagnosis, medical treatment, and prognosis of feline urolithiasis.

Radiographic or ultrasonographic evaluation of the urinary tract is required to consistently detect feline uroliths. Evaluation of clinical, laboratory, and radiographic findings facilitate "guesstimation" of the mineral composition of uroliths. Therapy should not be initiated before appropriate samples have been collected for diagnosis. The objectives of medical management of uroliths are to arrest further growth and to promote urolith dissolution by correcting or controlling underlying abnormalities. For therapy to be effective, it must induce undersaturation of urine with calculogenic crystalloids by (1) increasing the solubility of crystalloids in urine, (2) increasing the volume of urine in which crystalloids are dissolved or suspended, and (3) reducing the quantity of calculogenic crystalloids in urine.

Feline urolithiasis. Etiology and pathophysiology.

A variety of different types of uroliths occur in cats, of which calcium oxalate and magnesium ammonium phosphate are the most common. Treatment and prevention are most likely to be successful if associated risk factors are identified and eliminated or controlled.