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.     

Effects of dietary potassium citrate supplementation on urine pH and urinary relative supersaturation of calcium oxalate and struvite in healthy dogs

OBJECTIVE: To assess the effect of dietary potassium citrate supplementation on the urinary pH, relative supersaturation of calcium oxalate and struvite (defined as the activity product/solubility product of the substance), and concentrations of magnesium, ammonium, phosphate, citrate, calcium, and oxalate in dogs. ANIMALS: 12 healthy adult dogs. PROCEDURE: Canned dog food was fed to dogs for 37 days. Dogs were randomly allocated to 3 groups and fed test diets for a period of 8 days. Study periods were separated by 6-day intervals. During each study period the dogs were fed either standard diet solus (control) or standard diet plus 1 of 2 types of potassium citrate supplements (150 mg potassium citrate/kg of body weight/d) twice daily. Urinary pH, volume and specific gravity, relative supersaturation of calcium oxalate and struvite, and concentrations of magnesium, ammonium, phosphate, calcium, oxalate, and citrate were assessed for each treatment. RESULTS: Mean urine pH was not significantly affected by dietary potassium citrate supplementation, although urine pH did increase by 0.2 pH units with supplementation. Diets containing potassium citrate maintained a higher urine pH for a longer part of the day than control diet. Three Miniature Schnauzers had a significantly lower urinary relative calcium oxalate supersaturation when fed a diet supplemented with potassium citrate, compared with control diet. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary potassium citrate supplementation has limited effects on urinary variables in most healthy dogs, although supplementation results in maintenance of a higher urine pH later in the day. Consequently, if supplementation is introduced, dogs should be fed twice daily and potassium citrate should be given with both meals or with the evening meal only.     

The relative effects of supplemental dietary calcium and oxalate on urine composition and calcium oxalate relative supersaturation in healthy adult dogs

The aim of this study was to establish the relative effects of dietary calcium and oxalate (in the form of oxalic acid) on the composition of urine produced by healthy adult Cairn Terriers and Miniature Schnauzers. A nutritionally complete dry dog food was fed to 7 dogs (4 Cairn terriers and 3 Miniature schnauzers) for 24 weeks. The dogs were fed the diet alone, or supplemented with six different combinations of dietary calcium (as carbonate and sulphate) and oxalate (as oxalic acid) commonly found in dry commercially prepared dog foods. Urine pH, volume, specific gravity, and concentrations of 12 analytes were measured for each dog; urinary relative supersaturation (RSS) with calcium oxalate (CaOx) was calculated from these values. The effects of supplemental calcium and oxalate were established using two-way analysis of variance and multiple range tests (least significant difference); P<0.05 was considered significant. The lowest level of dietary calcium and oxalate resulted in the lowest CaOx RSS. The high calcium, low oxalate diet resulted in the highest CaOx RSS, a low calcium diet with increased dietary oxalate also tended to increase CaOx RSS although results were highly variable. Urinary calcium concentration increased significantly with dietary calcium; urinary oxalate increased, although inconsistently, with dietary oxalic acid only when dietary calcium was low. Measures to reduce both calcium and oxalate should be considered when implementing dietary changes to reduce the risk of calcium oxalate formation in dogs. A reduction in dietary calcium without a concomitant decrease in dietary oxalate may increase the risk of CaOx crystallisation in susceptible dogs.     

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.     

Effects of dietary supplementation with sodium chloride on urinary relative supersaturation with calcium oxalate in healthy dogs

OBJECTIVE: To evaluate the effect of dietary supplementation with sodium chloride (NaCl) on urinary calcium excretion, urine calcium concentration, and urinary relative supersaturation (RSS) with calcium oxalate (CaOx). ANIMALS: 6 adult female healthy Beagles. PROCEDURE: By use of a crossover study design, a canned diet designed to decrease CaOx urolith recurrence with and without supplemental NaCl (i.e., 1.2% and 0.24% sodium on a dry-matter basis, respectively) was fed to dogs for 6 weeks. Every 14 days, 24-hour urine samples were collected. Concentrations of lithogenic substances and urine pH were used to calculate values of urinary RSS with CaOx. RESULTS: When dogs consumed a diet supplemented with NaCl, 24-hour urine volume and 24-hour urine calcium excretion increased. Dietary supplementation with NaCl was not associated with a change in urine calcium concentration. However, urine oxalate acid concentrations and values of urinary RSS with CaOx were significantly lower after feeding the NaCI-supplemented diet for 28 days. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary supplementation with NaCl in a urolith-prevention diet decreased the propensity for CaOx crystallization in the urine of healthy adult Beagles. However, until long-term studies evaluating the efficacy and safety of dietary supplementation with NaCl in dogs with CaOx urolithiasis are preformed, we suggest that dietary supplementation with NaCl be used cautiously.     

Effect of dietary moisture and sodium content on urine composition and calcium oxalate relative supersaturation in healthy miniature schnauzers and labrador retrievers

The aim of this series of studies was to evaluate two possible feeding strategies as methods for reducing the risk of calcium oxalate (CaOx) formation in two breeds of healthy dog. The studies compared the effect of dietary moisture (Study 1) and dietary sodium (Na), (Study 2) on urine composition of labrador retrievers (LR) and miniature schnauzers (MS). A nutritionally complete dry dog food was fed to 16 dogs (eight LR, eight MS; Study 1) and 15 dogs (seven LR, eight MS; Study 2) for 24 days (Study 1), or 36 days (Study 2). The dogs were fed the diet alone (7% moisture, 0.06 g Na/100 kcal), or supplemented with deionised water to 73% moisture (Study 1), or dietary Na, to deliver 0.20 or 0.30 g Na per 100 kcal (Study 2). Urine pH, volume, specific gravity, and concentrations of 12 analytes were measured for each dog. Urinary relative supersaturations (RSS) with CaOx were calculated from these values. The effects of supplemental Na or water were established using t tests (Study 1) or analysis of variance, and multiple range tests (least significant difference) (Study 2); P<0.05 was considered significant. Increasing dietary moisture significantly increased total moisture intake (P=0.001), and reduced urine specific gravity (P=0.003), urinary oxalate concentration (P=0.04), and CaOx relative supersaturation (P=0.04) in the MS. Urinary parameters remained unchanged in the LR, indicating that feeding a high moisture diet may reduce the risk of CaOx formation in high-risk breeds. Increasing dietary Na led to production of urine with a significantly lower CaOx RSS in both breeds, indicating that sodium supplementation to dry diet formats may reduce the risk of CaOx formation. These feeding strategies should be considered when evaluating methods for preventing CaOx formation within high-risk groups.     

Risk factor analysis and relative supersaturation as tools for identifying calcium oxalate stone-forming dogs

Twenty-four hour urine samples were collected from 17 calcium oxalate (CaOx) stone-forming (SF) dogs and 17 normal (N), age-, breed- and sex-matched dogs. Urinary CaOx relative supersaturation (RSS) was calculated and found to be significantly higher in the SF group than the N group. RSS measurement is not readily applicable to veterinary practice; thus, alternatives were explored. Discriminant analysis failed to identify key factors differentiating most SF from N dogs. Urinary calcium, oxalate and uric acid, which differed between the SF and N animals, were combined into a measure of relative probability of CaOx stone formation (PSF) to establish whether this approach could be used to assess the risk of CaOx stone formation in dogs. Although there was good correlation between the techniques, RSS more clearly discriminated between SF and N dogs. These data suggest that neither PSF nor discriminant analysis is preferable to RSS for assessing the risk of CaOx stone formation in dogs.     

Echocardiographic parameters in healthy young adult Sphynx cats

The objective of this retrospective study is to determine normal reference values for 2-Dimension (2D) and Motion-mode (M-mode) echocardiographic parameters in nonsedated healthy young adult Sphynx cats and to compare them to those of the domestic shorthair (DSH). 131 Sphynx cats underwent cardiac screening prior to breeding. The control group consisted of 30 healthy adult domestic cats. A complete cardiac ultrasound was performed on all cats using right parasternal long and short axis views. There were few echocardiographic parameters in the Sphynx that differed from those of the healthy DSH. Only the left atrial (LA) dimension in 2D and M-mode, the left atrial/aortic (LA/Ao) ratio and the internal dimension of the left ventricle in systole (LVIDs) measured with M-mode were different. In conclusion, although the heart of Sphynx cat can often have a particular 2-D echocardiographic appearance, the M-mode cardiac dimensions are similar to those of the DSH.     

Substitution of dietary calcium chloride for calcium carbonate reduces urinary ph and urinary phosphorus excretion in adult cats

Summary

In a 4×4‐vvk cross‐over study, eight adult cats were given four moist diets containing identical amounts of calcium (13.9 mmol/MJ) but with different ratios of calcium carbonate to calcium chloride, the calcium salts providing half of the total dietary calcium. Increasing amounts of calcium chloride were substituted for equimolar amounts of calcium carbonate. Higher intakes of calcium chloride caused significantly lower pH values in postprandial and 24‐h urine samples. The urinary excretion of ammonium and titratable acid rose with increasing calcium chloride intake. The urinary concentrations of calcium and magnesium were not affected by the type of calcium salt, but the urinary excretion and concentration of phosphorus were significantly depressed when the amount of calcium chloride in the diet was increased. The results are discussed in the context of dietary prevention of and therapy for struvite urolithiasis in cats.     

Trends in the frequency of calcium oxalate uroliths in the upper urinary tract of cats

Medical records from cats diagnosed with uroliths at nine United States veterinary teaching hospitals from 1980 to 1999, and records of cats with uroliths submitted for analyses to the Minnesota Urolith Center from 1981 to 2000, were evaluated. A 10-fold increase in frequency of upper tract uroliths occurred in cats during the 20-year interval at the nine veterinary teaching hospitals. Calcium oxalate emerged as the predominant mineral type in upper tract uroliths, having increased more than 50-fold during the study period. These results emphasize the need for increased awareness of the occurrence of upper urinary tract uroliths in cats.     

Obesity increases initial rate of fibrin formation during blood coagulation in domestic shorthaired cats

Obesity predisposes to a prothrombotic state in humans, but whether a similar state occurs in obese animals is unknown. The objective of the current study was to examine the effect of body fat percentage (BF) on haemostatic parameters including thromboelastography with tissue factor as activator (TF-TEG) in client owned indoor-confined physically inactive cats. Seventy-two cats were included following an initial thorough health examination, and a complete blood count, biochemistry panel, conventional coagulation panel and a TF-TEG analysis were performed with tissue factor (1:50,000) as activator. The cats were anaesthetized, and BF was measured using Dual-energy X-ray absorptiometry. Significant difference between lean (BF < 35%, n = 26), overweight (35% < BF < 45%, n = 28) and obese (BF > 45%, n = 18) cats was identified using ANOVA. The correlation between BF, serum leptin and total adiponectin, respectively, with individual TEG and conventional coagulation parameters was evaluated. Obese cats showed a faster rate of fibrin formation (TF-TEG(R), p < 0.05), and TF-TEG(R) was positively correlated with plasma leptin levels. Increasing BF did not affect other conventional coagulation or TF-TEG parameters. In conclusion, this study indicates a connection between body fat content and altered haemostasis, also in cats. Whether feline obesity causes a hypercoagulable state of clinical relevance should be further investigated.     

Changes in proportion of canine urinary calculi composed of calcium oxalate or struvite in specimens analyzed from 1981 through 2001

The objective of this report was to characterize 20-year changes in proportion of calcium oxalate (CaOx) calculi and struvite calculi in dogs, and associations with breed, age, and sex. In this retrospective study, results of analysis of urinary calculi from dogs were reviewed for specimens received between July 1, 1981, and December 31, 2001. Breed, sex, age, year of submission of the specimen, and mineral type(s) were analyzed statistically. CaOx or Struvite or both were contained in 18,966 of 20,884 (91%) specimens. For both sexes, a 20-year statistically significant increase was observed in the proportion of calculus specimens that contained CaOx. The increase in this proportion was greater in females (1% to 31%) than in males (18% to 82%). From 1998 to 2001, when proportions may have plateaued, the odds of specimens containing CaOx were markedly higher in 18 breeds, markedly lower in 5 breeds, and not significantly different in 13 breeds compared with crossbreds. For both sexes, a 20-year statistically significant decrease was observed in the proportion of calculus specimens that contained struvite. This decrease in proportion was greater for males (79-16%) than for females (97-68%). From 1998 to 2001, when proportions plateaued, the odds of calculi containing struvite were markedly lower in 20 breeds, markedly higher in 1 breed, and not significantly different in 15 breeds when compared with crossbreds. Breed, age, and sex were associated statistically with CaOx or struvite urolithiasis. In conclusion, there appears to have been a long-term increase in the proportion of specimens of canine urinary calculi that contain CaOx as well as a long-term decrease in the proportion of specimens of calculi that contain struvite for both male and female dogs. The rate of change appeared to begin leveling off in the period 1998 to 2001. The recent proportion of dogs with either CaOx- or struvite-associated urolithiasis may depend on breed, age, and sex, and on interactions among these 3 factors.     

Dietary and animal-related factors associated with the rate of urinary oxalate and calcium excretion in dogs and cats

This paper reports the results of a cohort study and randomised clinical trial (RCT) in cross-over design. In the cohort study, the range of urinary oxalate (Uox) and calcium (Uca) excretion was determined within a sample of the Dutch population of dogs and cats, and dietary and animal-related factors associated with these urine parameters were identified. Spot urine samples were collected from privately owned dogs (n=141) and cats (n=50). The RCT determined the effect of a commercial raw meat diet versus a dry diet on Uox and Uca excretion rate in 23 dogs. In the cohort study, Uox excretion ranged from 21.1 to 170.6 mmol oxalate/mol creatinine in dogs and 27.5 to 161.6 in cats. Urinary calcium excretion ranged from 3.4 to 462.8 mmol calcium/mol creatinine in dogs and 10.1 to 128.0 in cats. In dogs, increased Uox and Uca excretion was associated with (1) the intake of a dry diet as the primary source of energy, (2) receiving no snacks and (3) breed. Increased Uox excretion was associated with males as well. In cats, urine collection in anaesthetised subjects was identified as a confounder. In the RCT, feeding the dry diet resulted in higher Uox (P<0.001) and Uca (P=0.021) excretion rates in dogs.     

Visual and quantitative electroencephalographic analysis of healthy young and adult cats under medetomidine sedation

A study was designed to investigate the effect of medetomidine sedation on quantitative electroencephalography (q-EEG) in healthy young and adult cats to determine objective guidelines for diagnostic EEG recordings and interpretation. Preliminary visual examination of EEG recordings revealed high-voltage low-frequency background activity. Spindles, k-complexes and vertex sharp transients characteristic of sleep or sedation were superimposed on a low background activity. Neither paroxysmal activity nor EEG burst-suppression were observed. The spectral analysis of q-EEG included four parameters, namely, relative power (%), and mean, median and peak frequency (Hz) of all four frequency bands (delta, theta, alpha and beta). The findings showed a prevalence of slow delta and theta rhythms as opposed to fast alpha and beta rhythms in both young (group A) and adult (group B) cats. A posterior gradient was reported for the theta band and an anterior gradient for the alpha and beta bands in both groups, respectively. The relative power value in group B compared to group A was significantly higher for theta, alpha and beta bands, and lower for the delta band. The mean and median frequency values in group B was significantly higher for delta, theta and beta bands and lower for the alpha band. The study has shown that a medetomidine sedation protocol for feline EEG may offer a method for investigating bio-electrical cortical activity. The use of q-EEG analysis showed a decrease in high frequency bands and increased activity of the low frequency band in healthy cats under medetomidine sedation.     

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.     

Mixed urolith (struvite and calcium oxalate) in a ferret (Mustela putorius furo)

Urolithiasis has been reported in veterinary literature in some species of the Mustelidae family, including ferrets. In this species, the most common form of urolithiasis is that caused by struvite. The current study examined the case of mixed urolith in an 8-month-old female ferret (Mustela putorius furo) with antecedents of strangury and hematuria. A cystotomy was carried out to remove the urolith, which had a rough surface and a homogeneously porous interior and was formed by a mixture of struvite (60%) and calcium oxalate dehydrated (40%).     

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.     

Studies on the pharmacokinetics and pharmacodynamics of mirtazapine in healthy young cats

Mirtazapine pharmacokinetics was studied in 10 healthy cats. Blood was collected before, and at intervals up to 72 h after, oral dose of 3.75 mg (high dose: HD) or 1.88 mg (low dose: LD) of mirtazapine. Liquid chromatography coupled to tandem mass spectrometry was used to measure mirtazapine, 8-hydroxymirtazapine and glucuronide metabolite concentrations. Noncompartmental pharmacokinetic modeling was performed. Median half-life was 15.9 h (HD) and 9.2 h (LD). Using Mann-Whitney analysis, a statistically significant difference between the elimination half-life, clearance, area under the curve (AUC) per dose, and AUC(∞) /dose of the groups was found. Mirtazapine does not appear to display linear pharmacokinetics in cats. There was no significant difference in glucuronidated metabolite concentration between groups. Pharmacodynamics was studied in 14 healthy cats administered placebo, LD and HD mirtazapine orally once in a crossover, blinded trial. In comparison with placebo, cats ingested significantly more food when mirtazapine was administered. No difference in food ingestion was seen between HD and LD, but significantly more behavior changes were seen with the HD. Limited serum sampling during the pharmacodynamic study revealed drug exposure comparable with the pharmacokinetic study, but no correlation between exposure and food consumed. Mirtazapine (LD) was administered daily for 6 days with no drug accumulation detected.     

Hypercalcemia and calcium oxalate urolithiasis in cats: a report of five cases.

Five cats that presented for signs of lower urinary tract disease (i.e., pollakiuria and hematuria) secondary to a calcium oxalate urolithiasis are presented. On evaluation, all five cats had elevations of both serum ionized as well as total serum calcium. The hypercalcemia resolved after discontinuation of urinary acidifying therapy or a dietary change, or both.