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Abstract

Objective

To evaluate the effects of dilution and alkalinization, separately and together, on the stability of uric acid in canine urine stored at −20 C.

Design

Prospective-controlled study.

Animals

5 dogs with confirmed ammonium urate uroliths, 6 Beagles, and 6 mixed-breed dogs.

Procedure

Dogs were fed a 31.4% protein (dry weight), meat-based diet for 21 days, and urine samples were collected on day 22. Urine samples were preserved, using combinations of dilution and alkalinization, and divided into 1-ml aliquots for storage at −20 C for 1 to 12 weeks. Urine uric acid concentrations were measured, using high-performance liquid chromatography, on day of collection (baseline), and after 1, 2, 4, 8, and 12 weeks.

Results

Alkalinization did not have a significant effect on reproducibility of measurements of uric acid concentrations in urine; however, dilution did have a significant effect. Compared with baseline, uric acid concentrations in urine samples collected from dogs with ammonium urate uroliths and Beagles and diluted 1:10 or 1:20 with deionized water were not different after storage for 1 to 12 weeks. Uric acid concentrations in urine samples collected from mixed-breed dogs did not differ from baseline values during the 12-week storage period whether samples were undiluted or were diluted 1:10 or 1:20 with deionized water.

Conclusions

Measurements of uric acid concentration are most reproducible in canine urine samples stored at −20 C for 1 to 12 weeks when samples are diluted 1:20 with deionized water.

Clinical Relevance

To ensure reproducibility of measurements of uric acid concentration in urine samples collected from dogs affected with urate uroliths, urine should be diluted 1:20 with deionized water. Alkalinization is not necessary, and is not recommended because of the additional step in processing and its potential to interfere with measurement of other urinary analytes. (Am J Vet Res 1996;57:787–790)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate the influence of 3 diets used to dissolve or prevent ammonium urate uroliths in dogs, and a diet formulated for growth, on 24-hour excretions of uric acid, ammonia, net acid, titratable acid, bicarbonate, and creatinine: 24-hour urine volumes: pH values of 24-hour urine samples; plasma uric acid concentration; serum creatinine concentration; and endogenous creatinine clearance values.

Design

Randomized block.

Animals

Six reproductively intact female Beagles, 3.9 to 4.2 years old, weighing 8.5 to 11.1 kg.

Procedures

Four diets were evaluated for their ability to dissolve magnesium ammonium phosphate hexahydrate (struvite) uroliths (diet S); to minimize uric acid excretion (diet U); to minimize clinical signs associated with renal failure (diet K); and to promote growth in pups (diet P). Each diet was fed for 14 days; then 24-hour urine samples were collected. An adult maintenance diet was fed during a 7-day washout period.

Results

Consumption of diet U was associated with lowest plasma uric acid concentration, lowest 24-hour urinary uric acid, ammonia, titratable acid, and net acid excretions, lowest endogenous creatinine clearance values, highest 24-hour urinary bicarbonate excretion and urine pH values, and highest 24-hour urine volumes. Consumption of diet P was associated with opposite results; results of consumption of diets S and K were intermediate between those for diets U and P.

Conclusion

Consumption of diet U by healthy Beagles is associated with reduced magnitude of urinary excretion of uric acid and ammonia, with alkaluria, and with polyuria, which may be beneficial in the management of ammonium urate uroliths in dogs.

Clinical Relevance

Results support use of diet U for management of ammonium urate urolithiasis in dogs.(Am J Vet Res 1996;57:324-328)

Free access
in American Journal of Veterinary Research

Abstract

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. (Am J Vet Res 1997;58:118–120)

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in American Journal of Veterinary Research

Abstract

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 leastsquares, 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. (Am J Vet Res 1997;58:511–515)

Free access
in American Journal of Veterinary Research

SUMMARY

Hyperxanthinuria and xanthine uroliths have been recognized with increased frequency in dogs with ammonium urate uroliths that had been given allopurinol. We hypothesized that dietary modification might reduce the magnitude of uric acid and xanthine excretion in urine of dogs given allopurinol. To test this hypothesis, excretion of metabolites, volume, and pH were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of allopurinol administration (15 mg/kg of body weight, PO, q 12 h) and consumption of 2 special purpose diets: a 10.4% protein (dry matter), casein-based diet and a 31.4% protein (dry matter), meat-based diet.

Significantly lower values of uric acid (P = 0.004), xanthine (P = 0.003), ammonia (P = 0.0002), net acid (P = 0.0001), titratable acid (P = 0.0002), and creatinine (P = 0.01) excreted during a 24-hour period were detected when dogs consumed the casein-based diet and were given allopurinol, compared with the 24-hour period when the same dogs consumed the meat-based diet and were given allopurinol. For the same 24-hour period, urine pH values, urine volumes, and urine bicarbonate values were significantly (P = 0.0004, P = 0.04, and P = 0.002, respectively) higher during the period when the dogs were fed the casein-based diet and given allopurinol than when they were fed the meat-based diet and given allopurinol. Endogenous creatinine clearance was significantly (P = 0.006) lower when dogs were fed the casein-based diet and given allopurinol than when they were fed the meat-based diet and given allopurinol. Significantly lower concentrations of plasma uric acid (P = 0.0001), plasma xanthine (P = 0.01), and serum urea nitrogen (P = 0.0001) were detected when dogs consumed the casein-based diet and were given allopurinol than when they consumed the meat-based diet and were given allopurinol. On the basis of these results, use of the casein-based diet and allopurinol in protocols designed for dissolution of urate uroliths may be beneficial in preventing hyperxanthinuria and xanthine urolith formation.

Free access
in American Journal of Veterinary Research

Summary

Urine uric acid-to-urine creatinine ratios (uua:uc), urine uric acid concentrations, urine uric acid concentrations corrected for glomerular filtration rate, and urinary uric acid fractional excretions were compared with 24-hour urinary uric acid excretions measured in 6 healthy adult female Beagles. Comparisons, using correlation analysis, were made when dogs consumed a 10.4% protein (dry weight), casein-based diet and a 31.4% protein (dry weight), meat-based diet. The uua:uc, urine uric acid concentrations corrected for glomerular filtration rate, and urinary uric acid fractional excretions were not reliable estimates of 24-hour urinary uric acid excretions during consumption of either diet. Urine uric acid concentrations in samples collected 2, 4, 6, and 24 hours after initiation of collection correlated with 24-hour urinary uric acid excretions when dogs consumed the casein-based diet; correlation was not found at any time interval when dogs consumed the meatbased diet. Therefore, determination of 24-hour urinary uric acid excretion is recommended because uua:uc are unreliable.

Free access
in American Journal of Veterinary Research

Abstract

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. (Am J Vet Res 1997;58:504–510)

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in American Journal of Veterinary Research

SUMMARY

Casein has been used as a protein source in diets designed to dissolve canine ammonium urate uroliths and to prevent their recurrence, because it contains fewer purine precursors than do many other sources of protein. However, an important question is whether reduced quantities of dietary casein have any benefit in modifying saturation of urine with urates. To answer this question, activity productd ratios of uric acid, sodium urate, and ammonium urate were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of consumption of a 10.4% protein, casein-based (10.4% casein) diet and a 20.8% protein, casein-based (20.8% casein) diet. Significantly lower activity product. ratios of uric acid, sodium urate, and ammonium urate were observed when dogs consumed the 10.4% casein diet. Significantly lower 24-hour urinary excretions of ammonia and phosphorus were observed when dogs consumed the 10.4% casein diet. Twenty-four-hour urinary excretions of magnesium and 24-hour urine pH values were significantly higher when dogs were fed the 10.4% casein diet. These results suggest that use of the 10.4% casein diet in protocols designed for dissolution and prevention of uric acid, sodium urate, and ammonium urate uroliths in dogs may be beneficial.

Free access
in American Journal of Veterinary Research

SUMMARY

Urine activity product ratios of uric acid, sodium urate, and ammonium urate and urinary excretion of metabolites were determined in 24-hour samples produced by 6 healthy Beagles during periods of consumption of a low-protein, casein-based diet (diet A) and a high-protein, meat-based diet (diet B). Comparison of effects of diet A with those of diet B revealed: significantly lower activity product ratios of uric acid (P = 0.025), sodium urate (P = 0.045), and ammonium urate (P = 0.0045); significantly lower 24-hour urinary excretion of uric acid (P = 0.002), ammonia (P = 0.0002), sodium (P = 0.01), calcium (P = 0.005), phosphorus (P = 0.0003), magnesium (P = 0.01), and oxalic acid (P = 0.004); significantly (P = 0.0001) higher 24-hour urine pH; and significantly (P = 0.01) lower endogenous creatinine clearance. These results suggest that consumption of diet A minimizes changes in urine that predispose dogs to uric acid, sodium urate, and ammonium urate urolithiasis.

Free access
in American Journal of Veterinary Research

SUMMARY

Urine activity product ratios of uric acid (aprua), sodium urate (aprna), and ammonium urate (aprau), and urinary excretion of 10 metabolites were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of consumption of 4 diets containing approximately 11% protein (dry weight) and various protein sources: a 72% moisture, casein-based diet; a 10% moisture, egg-based diet; a 72% moisture, chicken-based diet; and a 71% moisture, chicken-based, liver-flavored diet. Significantly (P < 0.05) higher aprua, aprna, and aprau were observed when dogs consumed the egg-based diet, compared with the other 3 diets; there were no differences in these ratios among the other 3 diets.

Twenty-four-hour urinary excretions of chloride, potassium, phosphorus, and oxalic acid were significantly (P < 0.05) higher when dogs consumed the egg-based diet. Twenty-four-hour urinary excretions of sodium were significantly (P < 0.05) higher when dogs consumed the egg-based diet, compared with the casein-based diet and the chicken-based, liver-flavored diet, but were not significantly different between the egg-based diet and chicken-based diet. Twenty-four-hour urine volume was similar when dogs consumed the 4 diets. Twenty-four-hour endogenous creatinine clearance was significantly (P < 0.05 lower when dogs consumed the casein based diet there were no differences among the other 3 diets. Although consumption all diets was associated with production alkaline urine, the 24-hour urine pH was significantly (P < 0.05) higher when dogs consumed the egg-based diet.

These results suggest that use diets containing approximately 10.5% protein (dry weight) and 70 moisture protocols designed for dissolution and prevention urate uroliths may be beneficial. The source dietary protein in canned formulated diets does not appear significantly influence the saturation of urine with uric acid, sodium urate, or ammonium urate.

Free access
in American Journal of Veterinary Research