Plasma and Whole Blood Taurine Concentrations in Dogs May Not Be Sensitive Indicators of Taurine Deficiency When Dietary Sulfur Amino Acid Content Is Reduced.

Background: Taurine status is impacted by dietary supply of methionine and cysteine (SAA) and possibly intestinal microbial activity, where plasma and whole blood taurine concentrations are currently used to evaluate taurine status. Objective: We determined effects of dietary SAA restriction on rate and extent of taurine depletion of blood and skeletal muscle in dogs of two body sizes, and whether oral antibiotic administration affected the taurine depletion and fecal bile acid excretion of the dogs. Methods: Adult, male, Beagles (n = 6; 10.1-13.1 kg) and larger mixed-breed dogs (n = 6; 28.5-41.1 kg) were given four dry-expanded diets, whereby each successive diet contained lower protein and/or SAA concentration. After receiving the final diet for 44 weeks, all dogs were orally administered a mixture of ampicillin, neomycin sulfate, and metronidazole for 12 weeks. Taurine concentrations were determined every 2-4 weeks in venous blood and voided urine and every 4 to 16 weeks in biopsied semimembranosus muscle. Fecal bile acid excretion before and after antibiotics administration were quantified. Results: When given for 36 weeks the lowest SAA diet, 3.4% methionine and 2.9% cystine, taurine concentrations in whole blood were not different between groups, while taurine in plasma declined (P < 0.05) in large but not in small dogs, and taurine in biopsied muscle decreased (P < 0.05) by 50% in large and by 37% in small dogs. Concentrations of taurine in muscle were lower (P < 0.01) and fecal bile acids greater (P = 0.001) in large than small dogs. Antibiotic administration restored plasma and muscle taurine to initial concentrations and halved fecal bile acid excretion by dogs of both groups. Conclusions: Blood taurine concentration may not be a sensitive indictor of taurine depletion caused by low intake of bioavailable SAA in dogs, especially in large dogs. Taurine status and dietary SAA requirements of dogs may substantively depend on taurine loss mediated by intestinal microbiota.

Clinical progression of cats with early-stage chronic kidney disease fed diets with varying protein and phosphorus contents and calcium to phosphorus ratios.

BACKGROUND: Dietary protein and phosphorus (P) restriction is the mainstay for nutritional management of chronic kidney disease (CKD). However, adequate restriction levels for cats with early CKD remain unclear. OBJECTIVES: To investigate responses in cats with early CKD to varying dietary protein, P, and calcium (Ca) : P ratio. ANIMALS: Nineteen research colony cats with International Renal Interest Society stages 1-2 CKD. METHODS: In an opportunistic longitudinal case study, cats were fed a low protein (59 g/Mcal), low P (0.84 g/Mcal) dry diet (LP-LP; Ca : P = 1.9) for 18 months and later transitioned onto a moderate protein (76-98 g/Mcal), moderate P (1.4-1.6 g/Mcal) dry-wet diet regimen (MP-MP; Ca : P = 1.4-1.6) for 22 months. Fold-changes in serum creatinine, total Ca (tCa) and P (primary outcomes) and fibroblast growth factor 23 (FGF23) were assessed by linear-mixed models. RESULTS: While feeding LP-LP, mean serum creatinine decreased (0.87-fold, 95% confidence interval [CI] 0.81, 0.93, P < .001) to within reference range after 6 months, while increases in total Ca (tCa; 1.16-fold, 95% CI 1.11, 1.22, P < .001) and FGF23 (2.72-fold, 95% CI 1.72, 4.31, P < .001), but not in P (1.03-fold, 95% CI 0.945, 1.124, P = .94), were observed after 17 months. On MP-MP, mean creatinine, tCa and P remained within reference ranges and did not significantly change (P = .11, P = .98, and P = 1, respectively), while FGF23 significantly decreased (0.58-fold, 95% CI 0.36, 0.95, P = .02) after 22 months. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with early CKD developed hypercalcemia after long-term feeding of a highly P-restricted diet. Increasing dietary P and reducing Ca : P ratio maintained renal markers, while improving Ca-P balance. Cats with early CKD could benefit from moderately protein- and P-restricted diets.

Towards establishing no observed adverse effect levels (NOAEL) for different sources of dietary phosphorus in feline adult diets: results from a 7-month feeding study.

High dietary phosphorus (P), particularly soluble salts, may contribute to chronic kidney disease development in cats. The aim of the present study was to assess the safety of P supplied at 1 g/1000 kcal (4184kJ) from a highly soluble P salt in P-rich dry format feline diets. Seventy-five healthy adult cats (n 25/group) were fed either a low P control (1·4 g/1000 kcal [4184kJ]; Ca:P ratio 0·97) or one of two test diets with 4 g/1000 kcal (4184 kJ); Ca:P 1·04 or 5 g/1000 kcal (4184kJ); Ca:P 1·27, both incorporating 1 g/1000 kcal (4184 kJ) sodium tripolyphosphate (STPP) - for a period of 30 weeks in a randomised parallel-group study. Health markers in blood and urine, glomerular filtration rate, renal ultrasound and bone density were assessed at baseline and at regular time points. At the end of the test period, responses following transition to a commercial diet (total P - 2·34 g/1000 kcal [4184kJ], Ca:P 1·3) for a 4-week washout period were also assessed. No adverse effects on general, kidney or bone (skeletal) function and health were observed. P and Ca balance, some serum biochemistry parameters and regulatory hormones were increased in cats fed test diets from week 2 onwards (P ≤ 0·05). Data from the washout period suggest that increased serum creatinine and urea values observed in the two test diet groups were influenced by dietary differences during the test period, and not indicative of changes in renal function. The present data suggest no observed adverse effect level for feline diets containing 1 g P/1000 kcal (4184 kJ) from STPP and total P level of up to 5 g/1000 kcal (4184 kJ) when fed for 30 weeks.

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 High-Fat Diet at Two Energetic Levels on Fecal Microbiota, Colonic Barrier, and Metabolic Parameters in Dogs.

Increased consumption of energy-rich foods is a key factor in overweight, obesity, and associated metabolic disorders. This would be, at least in part, related to microbiota disturbance. In rodent models of obesity, microbiota disruption has been associated with alteration of the intestinal barrier, endotoxemia, inflammation grade, and insulin sensitivity. The aim of the present study was to assess the effects of a high-fat diet (HFD), fed at two energetic levels, on microbiota, intestinal barrier, and inflammatory and metabolic parameters in dogs. A HFD (33% fat as fed, 4,830 kcal/kg) was given to 24 healthy Beagle dogs at 100% (HF-100; n = 8) and at 150% (HF-150; n = 16) of their maintenance energy requirements for 8 weeks. Analysis of similarity revealed a significant difference in gut microbiota ß-diversity following the diet compared to week 0 in both groups while α-diversity was lower only in the HF-150 group. Firmicutes/Bacteroidetes ratio was higher in the HF-150 group compared to the HF-100 group at weeks 2 and 8. A reduction in insulin sensitivity was observed over time in the HF150 group. Neither endotoxemia nor inflammation was observed in either group, did not find supporting data for the hypothesis that the microbiota is involved in the decline of insulin sensitivity through metabolic endotoxemia and low-grade inflammation. Colonic permeability was increased at week 4 in both groups and returned to initial levels at week 8, and was associated with modifications to the expression of genes involved in colonic barrier function. The increase in intestinal permeability may have been caused by the altered intestinal microbiota and increased expression of genes encoding tight junction proteins might indicate a compensatory mechanism to restore normal permeability. Although simultaneous changes to the microbiota, barrier permeability, inflammatory, and metabolic status have not been observed, such a causal link cannot be excluded in dogs overfed on a HFD. Further studies are necessary to better understand the link between HFD, intestinal microbiota and the host.

Increasing dietary sodium chloride promotes urine dilution and decreases struvite and calcium oxalate relative supersaturation in healthy dogs and cats.

Urolithiasis is highly prevalent in dogs and cats, with struvite and calcium oxalate being most commonly diagnosed. Some commercial diets aimed at reducing the risk of urolithiasis are based on inclusion of sodium chloride (NaCl) in an attempt to dilute the urine and the risk of crystallization, but more information on the effect of differing levels of sodium inclusion is needed. The objective of this study was to compare the short-term effect of four diets differing only in NaCl content (base diet with 0.3% sodium and diets with added NaCl to achieve 0.7, 1.0 and 1.3% sodium as fed) on urinary ion concentrations and relative supersaturation (RSS) of struvite and calcium oxalate in dogs and cats. In both species, there was a significant increase in water intake and urine volume as dietary NaCl increased. Urine sodium concentration increased with increasing dietary NaCl. The highest sodium diet increased urinary calcium excretion in dogs only, while decreasing urinary calcium concentration. Calcium oxalate RSS and struvite RSS both significantly decreased, with the lowest RSS values reported on the highest sodium diet in both dogs and cats (p < .001). These results suggest that an increase in dietary NaCl decreases RSS values in both dogs and cats. Despite an increase in urinary calcium excretion in dogs, urinary calcium concentration and calcium oxalate RSS were lower on high sodium diets due to urine dilution. Long-term studies are needed to confirm the relationship between RSS and stone occurrence and recurrence.

Fibroblast growth factor 23 and symmetric dimethylarginine concentrations in geriatric cats.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is increased in azotemic cats with chronic kidney disease (CKD) and predictive of the onset of azotemia in older cats. The introduction of symmetric dimethylarginine (SDMA) as a biomarker of glomerular filtration rate has led to the identification of cats in which SDMA is increased, but plasma creatinine concentrations remains within reference range. There is currently little understanding of the metabolic changes present in such cats. OBJECTIVES: To examine the relationship between plasma FGF23 and SDMA concentrations in non-azotemic geriatric cats. ANIMALS: Records of a cross section of client-owned cats (n = 143) without azotemic CKD. METHODS: Clinicopathological information was obtained from cats (≥ 9 years) from records of 2 first opinion practices. The relationship between plasma SDMA and FGF23 concentrations was examined using Spearman's correlation and variables compared using the Mann-Whitney U test. RESULTS: Cats with increased SDMA concentrations had significantly higher plasma FGF23 (P < .001) and creatinine (P < .001) concentrations compared to cats with SDMA concentrations within reference range. A weak positive relationship was demonstrated between plasma FGF23 and SDMA concentrations (r = .35, P < .001) and between plasma FGF23 and creatinine (r = .23, P = .005) concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: More cats with increased SDMA concentrations had higher FGF23 concentrations than those with SDMA concentrations within the reference range, suggesting the presence of an alteration in phosphate homeostasis. Further studies are warranted to identify influencing factors and to explore the utility of FGF23 concentration to inform management of cats with early stage CKD.

Nutritional management of inherited copper-associated hepatitis in the Labrador retriever.

Canine hereditary copper-associated hepatitis is characterized by gradual hepatic copper accumulation eventually leading to liver cirrhosis. Therapy is aimed at creating a negative copper balance with metal chelators, of which D-penicillamine is the most commonly used. D-penicillamine often causes gastro-intestinal side effects and life-long continuous therapy may lead to a deficiency of copper and zinc. The aim of the current study was to investigate the effect of a low-copper, high-zinc diet as an alternative to continuous D-penicillamine treatment for the long-term management of canine copper-associated hepatitis. Sixteen affected Labrador retrievers were followed for a median time period of 19.1 months (range, 5.9-39 months) after being effectively treated with D-penicillamine. The dogs were maintained on a diet containing 1.3±0.3 mg copper/1000 kcal and 64.3±5.9 mg zinc/1000 kcal. Liver biopsies were taken every 6 months for histological evaluation and copper determination. Plasma alanine aminotransferase (ALT) and alkaline phosphatase, as well as serum albumin were determined. Dietary treatment alone was sufficient to maintain hepatic copper concentration below 800 mg/kg dry weight liver in 12 dogs during the study period. Four dogs needed re-treatment with D-penicillamine. ALT activity and albumin concentration were not associated with hepatic copper concentration, but showed a significant association with the stage and grade of hepatitis respectively. In conclusion, a low-copper, high-zinc diet can be a valuable alternative to continuous d-penicillamine administration for long-term management of dogs with copper-associated hepatitis. The copper re-accumulation rate of an individual dog should be considered in the design of a long-term management protocol and in determining re-biopsy intervals.

Evaluation of association between body size and large intestinal transit time in healthy dogs.

OBJECTIVE: To compare large intestinal transit time (LITT) in dogs of various body sizes and determine whether fecal quality was correlated with LITT. ANIMALS: 6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE: LITT was calculated as the difference between total (TTT) and orocecal transit time (OCTT). Minimum and mean OCTTs were determined by use of the sulfasalazine-sulfapyridine method. Minimum TTT was estimated by use of chromium and ferric oxide as color markers, and mean TTT was calculated from the recovery from feces of ingested colored plastic beads. Fecal moisture content was determined and fecal consistency was scored during the same period. RESULTS: Large-breed dogs had higher fecal moisture content and more watery fecal consistency. No association between body size and OCTT was detected, but there was a positive correlation between body size and mean TTT. Mean LITT increased significantly with body size, from 9.1 +/- 1.1 hours in Miniature Poodles to 39.4 +/- 1.6 hours for Giant Schnauzers. Significant correlations were detected among mean LITT, mean TTT, and fecal scores, whereas no correlation was observed between fecal moisture content and TTT or LITT. CONCLUSIONS AND CLINICAL RELEVANCE: LITT was correlated with fecal consistency in dogs of various body sizes. Mean LITT can be predicted from values for mean TTT in healthy dogs.

Effects of dietary fat and energy on body weight and composition after gonadectomy in cats.

OBJECTIVE: To evaluate the effect of dietary fat and energy density on body weight gain, body composition, and total energy expenditure (TEE) in neutered and sexually intact cats. ANIMALS: 12 male and 12 female cats PROCEDURE: Male cats were castrated (castrated male [CM]) or underwent no surgical procedure (sexually intact male [IM]). Female cats underwent ovariectomy (spayed female [SF]) or laparotomy and ligation of both uterine tubes without ovary removal (sexually intact female [IF]). Cats were fed either the low-fat (LF) or high-fat (HF) diet for 26 weeks, with the final allocation consisting of 8 groups: IF-LF IF-HE SF-LF, SF-HF IM-LF, IM-HF, CM-LF, and CM-HF. Mean food intake for each group was recorded daily, and body weight was monitored weekly throughout the study. Body composition and TEE were measured before surgery in week 0 and at the end of the study (week 26) by isotope dilution (double-labelled water). RESULTS: N eutered cats gained significantly more body fat and body weight (53.80+/-5.79%) than sexually intact cats (27.11+/-5.79%) during the study. Body weight gain of neutered cats fed the HF diet was greater than those fed the LF diet. Following correction for body composition, TEE was similar in all groups and no pattern towards increased food intake was evident. CONCLUSIONS AND CLINICAL RELEVANCE: Weight gain in neutered cats was decreased by feeding an LF, low energy-dense diet. To prevent weight gain in cats after neutering, a suitable LF diet should be fed in carefully controlled meals rather than ad libitum.

Influence of age and body size on orocecal transit time as assessed by use of the sulfasalazine method in healthy dogs.

OBJECTIVE: To compare orocecal transit time (OCTT) as assessed by use of the sulfapyridine appearance time in plasma after oral administration of sulfasalazine in dogs of varying age and body size and determine whether OCTT correlates with fecal quality. ANIMALS: 6 Miniature Poodles (MP), 6 Standard Schnauzers (SS), 6 Giant Schnauzers (GS), and 6 Great Danes (GD). PROCEDURE: Determinations of OCTT were made at 12, 22, 36, and 60 weeks of age. Dogs were fed sulfasalazine mixed with a meal. Blood samples were then collected for 6 hours. The OCTT was the time from ingestion of the meal to detection of sulfapyridine in plasma. Fecal moisture content and consistency were recorded during the same periods. RESULTS: Mean OCTT decreased during growth of GS and GD dogs. No correlation was found between OCTT and fecal variables during growth in the 4 breeds. Effect of body size was observed at 12 and 22 weeks of age, with a longer OCTT in GS and GD than in MP and SS dogs. Similar OCTTs were observed at 36 and 60 weeks of age in all breeds, although GS and GD dogs had poorer fecal quality during those periods. CONCLUSIONS AND CLINICAL RELEVANCE: An effect of age on OCTT was observed only in large-breed dogs, with longer transit times in puppies (12 weeks old) than in adults (60 weeks old). Mean OCTT is not correlated with body size in adult dogs. No relationship was detected between OCTT and fecal variables in healthy dogs.

Influence of age and body size on intestinal permeability and absorption in healthy dogs.

OBJECTIVE: To evaluate effects of age and body size of dogs on intestinal permeability (unmediated diffusion) as measured by the ratio of urinary lactulose to L-rhamnose (L:R) and absorption (carrier-mediated transport) as measured by the ratio of urinary D-xylose to 3-O-methyl-D-glucose (X:MG) and to determine whether these variables correlated with fecal quality. ANIMALS: 6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE: A solution that contained lactulose and rhamnose or xylose and 3-O-methyl-D-glucose was administered orally to dogs that were 12, 22, 36, and 60 weeks old. Urine was collected 6 hours later, and urinary L:R and X:MG were calculated. Fecal moisture and scoring were recorded during the same periods. RESULTS: Age and breed did not affect intestinal absorption, and we did not detect a relationship between X:MG and fecal variables. In contrast, we detected significant effects of age and body size on intestinal permeability. Puppies (12 weeks old) and large dogs had higher intestinal permeability than adult (60 weeks old) and small dogs. The increased intestinal permeability in large dogs was associated with lower fecal quality as indicated by the significant positive correlations between L:R and fecal moisture (r, 0.61) and L:R and fecal scores (r, 0.86) in adult dogs. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that age and body size should be considered when assessing intestinal permeability by use of the L:R urinary excretion test in dogs. High intestinal permeability could be a possible cause of poor fecal quality in large dogs.

Breath hydrogen concentrations of cats given commercial canned and extruded diets indicate gastrointestinal microbial activity vary with diet type.

Breath hydrogen (H(2)) concentration, an indicator of intestinal microbial abundance, was determined in cats given purified and commercial canned and dry-type diets. Before measurements, the cats were fed diets for more than 2 wk and habituated to a daily feeding interval of 4 hr. Breath H(2) concentrations were determined before a meal (approximately 25% daily MER) and then every 20 min for 8 hr or hourly for 10 hr. A clear rise above baseline breath H(2) concentrations, 1-2 ppm, was not observed in 6 males given a casein-based purified diet. A mean (+/- SEM) peak breath H(2) concentration of 22 +/- 4 ppm was observed in 6 other males, 6.3 hr after ingestion of a canned diet with protein, fat, and carbohydrate proportions similar to those of the purified diet. Area-under-the-curve (AUC) breath H(2) responses to the canned diet were substantially greater (p < 0.05) than responses observed in 5 males given a dry-type diet, but similar to responses observed in 12 males given an uncooked form of the canned diet. Gamma irradiation to inactivate microbes in the uncooked diet did not affect the breath H(2) response. Breath H(2) responses to 2 other canned and 2 other dry-type diets were evaluated in 8 adult females using a 4 x 4 Latin-square design. Peak and AUC responses to the canned diets were similar but approximately 2 times greater (p < 0.05) than responses to the dry diets. Relative to dry-type diets, canned diets induce a substantially greater breath H(2) production, and therefore appear to support a greater intestinal microbial population.

Influence of age and body size on gastrointestinal transit time of radiopaque markers in healthy dogs.

OBJECTIVE: To compare gastric emptying time, small-intestinal transit time (SITT), and orocecal transit time (OCTT) of radiopaque markers in dogs varying in age and body size and to determine whether fecal variables (ie, consistency and moisture content) are related to gastrointestinal tract transit times in dogs. ANIMALS: 24 eight-week-old female puppies, including 6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE: Gastrointestinal tract transit time experiments were performed at 12, 22, 36, and 60 weeks of age. Dogs were fed 30 small radiopaque markers mixed with a meal. Abdominal radiographs were taken. The time at which 50% of the markers had left the stomach (T50) and the time at which the first marker reached the colon were calculated. Fecal moisture content and scoring on the basis of fecal consistency were recorded during the same periods. RESULTS: Puppies had a shorter mean T50 than adults, and mean OCTT decreased significantly only during growth of large-breed dogs. However mean fecal moisture content significantly increased with age, except in Giant Schnauzers. No effect of body size on T50 was found regardless of age, and no difference was observed between OCTT of small- and large-breed adult dogs. The effect of age on the mean SITT was not significant for any breed. However, a strong positive correlation was recorded between body size and fecal moisture content (r2 = 0.77) or fecal scores (r2 = 0.69) in adult dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Age affects T50 in small- and large-breed dogs and OCTT in large-breed dogs. However, body size does not affect T50 or OCTT. A relationship does not exist between gastrointestinal tract transit time and fecal variables in healthy dogs.