Conserved signatures of the canine faecal microbiome are associated with metronidazole treatment and recovery.

Antibiotic resistance is recognised as one of the biggest global threats to human and animal health. Understanding the influence of antibiotics on the canine microbiome is important to know the potential mid-to-long term effects on dysbiosis and mitigate side-effects such as antibiotic-associated diarrhoea. In this study, metronidazole was prescribed to 22 dogs for suspected giardiasis after exhibiting gastrointestinal symptoms such as diarrhoea and/or vomiting. Faecal samples were collected before, during seven days of treatment, and six months post-cessation. Faecal microbiota was assessed with 16S rRNA sequencing. Shannon diversity was reduced for up to three days after the treatment ended, and an altered community persisted for four to six weeks. All dogs recovered to a similar microbiome composition as pre-treatment. Immediately after receiving metronidazole, an increase in the relative abundance of the genera Lactobacillus, Bifidobacterium, and Enterococcus was observed. This may be due to antibiotic resistance commonly exhibited by these organisms. One-to-two weeks post-cessation, several other genera that were sensitive to the antibiotic recovered in abundances, with taxa belonging to the Erysipelotrichaceae family particularly driving composition change. Many of the bacteria initially reduced were associated with carbohydrate fermentation. This suggests scope exists to explore interventions to augment gastrointestinal health and support the re-establishment of the microbiome.

Glycine supplementation can partially restore oxidative stress-associated glutathione deficiency in ageing cats.

Intracellular levels of glutathione, the major mammalian antioxidant, are reported to decline with age in several species. To understand whether ageing affects circulating glutathione levels in cats, blood was sampled from two age groups, < 3 years and > 9 years. Further, to determine whether dietary supplementation with glutathione precursor glycine (GLY) affects glutathione concentrations in senior cats (> 8 years), a series of free GLY inclusion level dry diets were fed. Subsequently, a 16-week GLY feeding study was conducted in senior cats (> 7 years), measuring glutathione, and markers of oxidative stress. Whole blood and erythrocyte total, oxidised and reduced glutathione levels were significantly decreased in senior cats, compared with their younger counterparts (P ≤ 0·02). The inclusion level study identified 1·5 % free GLY for the subsequent dry diet feeding study. Significant increases in erythrocyte total and reduced glutathione were observed between senior cats fed supplemented and control diets at 4 weeks (P ≤ 0·03; maximum difference of 1·23 µM). Oxidative stress markers were also significantly different between groups at 8 (P = 0·004; difference of 0·68 nG/ml in 8-hydroxy-2'-deoxyguanosine) and 12 weeks (P ≤ 0·049; maximum difference of 0·62 nG/mG Cr in F2-isoprostane PGF2α). Senior cats have lower circulating glutathione levels compared with younger cats. Feeding senior cats a complete and balanced dry diet supplemented with 1·5 % free GLY for 12 weeks elevated initial erythrocyte glutathione and altered markers of oxidative stress. Dietary supplementation with free GLY provides a potential opportunity to restore age-associated reduction in glutathione in cats.

Dietary Supplementation with Nucleotides, Short-Chain Fructooligosaccharides, Xylooligosaccharides, Beta-Carotene and Vitamin E Influences Immune Function in Kittens.

Nucleotides, short-chain fructooligosaccharides (scFOS), xylooligosaccharides (XOS), ß-carotene and vitamin E are reported to enhance immune function; however, the evidence of this in cats is limited. The aim of this study was to determine the immunomodulatory effects of these ingredients in kittens. Forty domestic short hair kittens were designated in litters to control or test diet for 28 weeks. Test diet was fortified with 0.33 g nucleotides, 0.45 g scFOS, 0.3 g XOS, 0.7 mg ß-carotene and 66.5 mg vitamin E per 100 g diet. Kittens were vaccinated against feline parvovirus (FPV) and herpesvirus (FHV) at 10, 14 and 18 weeks. Kittens remained healthy, with no measured evidence of adverse health. Serum FPV and FHV antibody titres were significantly (p < 0.05) higher in the test diet group at week 23 and 27, respectively. A significantly (p < 0.05) higher proportion of test diet group kittens demonstrated an adequate response (four-fold titre increase) to FHV vaccination and a significantly (p < 0.05) higher proportion reached a protective antibody titre for FHV. Serum IgM was significantly (p < 0.05) higher in the test diet group. The test diet group demonstrated a stronger humoral immune response to vaccination, suggesting the diet supports immune defence, enabling a greater response to immune challenges.

A Novel Prebiotic Fibre Blend Supports the Gastrointestinal Health of Senior Dogs.

Senior pets can suffer from a wide range of age-related diseases that can impact the quality of life for the pet and the relationship between a pet and their owner. Dietary fibre plays a key role in shaping the gastrointestinal health in mammalian species. The aim of this study was to investigate the impact of a novel prebiotic fibre blend containing sugar beet pulp, galacto-oligosaccharides, and cellulose on the health of senior dogs when fed on top of a background commercial dry diet. Thirty-two dogs aged >8 years received the prebiotic fibre blend as a dietary topper for 21 days on top of a nutritionally complete diet using a cross-over study design. The prebiotic fibre blend improved the gastrointestinal health of senior dogs as measured through improved faecal quality scores, a reduction in faecal pH, changes to the taxonomic composition of the gut, and a reduction in faecal branched-chain fatty acids, which are markers for proteolytic degradation. Broader systemic measures, such as changes to serum cytokines, were not impacted by the prebiotic fibre blend. In conclusion, a novel prebiotic fibre blend containing sugar beet pulp, galacto-oligosaccharides, and cellulose improved the gastrointestinal health of senior dogs and could have a range of potential future dietary applications.

The MARS PETCARE BIOBANK protocol: establishing a longitudinal study of health and disease in dogs and cats.

BACKGROUND: The veterinary care of cats and dogs is increasingly embracing innovations first applied to human health, including an increased emphasis on preventative care and precision medicine. Large scale human population biobanks have advanced research in these areas; however, few have been established in veterinary medicine. The MARS PETCARE BIOBANK™ (MPB) is a prospective study that aims to build a longitudinal bank of biological samples, with paired medical and lifestyle data, from 20,000 initially healthy cats and dogs (10,000 / species), recruited through veterinary hospitals over a ten-year period. Here, we describe the MPB protocol and discuss its potential as a platform to increase understanding of why and how diseases develop and how to advance personalised veterinary healthcare. METHODS: At regular intervals, extensive diet, health and lifestyle information, electronic medical records, clinicopathology and activity data are collected, genotypes, whole genome sequences and faecal metagenomes analysed, and blood, plasma, serum, and faecal samples stored for future research. DISCUSSION: Proposed areas for research include the early detection and progression of age-related disease, risk factors for common conditions, the influence of the microbiome on health and disease and, through genome wide association studies, the identification of candidate loci for disease associated genetic variants. Genomic data will be open access and research proposals for access to data and samples will be considered. Over the coming years, the MPB will provide the longitudinal data and systematically collected biological samples required to generate important insights into companion animal health, identifying biomarkers of disease, supporting earlier identification of risk, and enabling individually tailored interventions to manage disease.

Healthy cats tolerate long-term daily feeding of Cannabidiol.

Cannabidiol (CBD)-containing products are widely commercially available for companion animals, mirroring popularity in human use. Although data on the safety and efficacy of long-term oral supplementation are increasing in dogs, evidence remains lacking in cats. The purpose of these studies was to address gaps in the knowledge around the long-term suitability and tolerance of a tetrahydrocannabinol (THC)-free CBD distillate in clinically healthy cats. The studies were randomized, blinded, and placebo-controlled. The first study supplemented cats with either a placebo oil (n = 10) or with 4 mg/kg body weight (BW) CBD in placebo oil (n = 9) daily, with a meal, for 4 weeks. The concentration of CBD in plasma was measured over 4 h at d0 (first dose) and again at d14 (after 2 weeks of daily dosing). The second study supplemented cats daily with either placebo oil (n = 10) or 4 mg/kg BW CBD in placebo oil (n = 10) for a period of 26 weeks. A comprehensive suite of physiological health measures was performed throughout the study at baseline (week 0) and after 4, 10, 18, and 26 weeks of feeding, followed by a 4-week washout sample (week 30). Postprandial plasma CBD time course data, at both d0 and d14, showed a peak plasma CBD concentration at 2 h after the dose. This peak was 251 (95% CI: 108.7, 393.4) and 431 (95% CI, 288.7, 573.4) ng/mL CBD at d0 and d14, respectively, and the area under the curve concentration was higher by 91.5 (95% CI, 33.1, 149.9) ng-h/mL after 2 weeks of supplementation (p = 0.002). While in the first study the CBD group displayed increased alanine aminotransferase (ALT; 68.7 (95% CI, 43.23, 109.2) U/L) at week 4 compared to the placebo control group [1.44-fold increase (95% CI, 0.813, 2.54)], statistical equivalence (at 2-fold limits) was found for ALT across the duration of the second, long-term study. All other biochemistry and hematology data showed no clinically significant differences between supplement groups. Data presented here suggest that a THC-free, CBD distillate fed at a dose of 4 mg/kg BW was absorbed into plasma and well tolerated by healthy cats when supplemented over a period of 26 weeks.

Long-term daily feeding of cannabidiol is well-tolerated by healthy dogs.

Cannabidiol (CBD) containing dog food and treats are widely commercially available, mirroring the growing popularity of CBD as a supplement for humans. Despite this, experimental evidence of the safety and efficacy of long-term oral exposure in dogs is lacking. The purpose of this study was to address the gap in knowledge around the longer-term suitability and tolerance of a broad-spectrum CBD (THC-free) distillate in clinically healthy dogs. The study was a randomized, placebo-controlled, and blinded study where one group of twenty dogs received daily CBD capsules at a dose of 4 mg/kg of body weight (BW) for a period of 6 months. The control group of twenty dogs received placebo capsules. A comprehensive suite of physiological health measures was performed throughout the study at baseline, and after 2, 4, 10, 18, and 26 weeks of exposure, followed by 4 weeks of washout. CBD concentrations were measured at the same cadence in plasma, feces and urine. Health measures included biochemistry, hematology, urinalysis, in addition to fortnightly veterinary examinations, twice daily well-being observations, and a daily quality-of-life survey. Biochemistry and hematology showed no clinically significant alterations apart from a transient elevation in alkaline phosphatase (ALP) in just over half of the dogs receiving CBD. This elevation was observed in the absence of concurrent elevations of other liver parameters, and without any adverse effects on health and wellbeing. Furthermore, bone alkaline phosphatase (BALP) was simultaneously elevated with a significant, strong (r > 0.9) positive correlation between the two measures, suggesting that the elevation of total ALP was at least partly due to the bone-derived isoform. This study provides evidence that a once-daily oral dose of 4 mg CBD/kg BW is well tolerated in clinically healthy dogs for a duration of 6-months.

An early prediction model for canine chronic kidney disease based on routine clinical laboratory tests.

The aim of this study was to derive a model to predict the risk of dogs developing chronic kidney disease (CKD) using data from electronic health records (EHR) collected during routine veterinary practice. Data from 57,402 dogs were included in the study. Two thirds of the EHRs were used to build the model, which included feature selection and identification of the optimal neural network type and architecture. The remaining unseen EHRs were used to evaluate model performance. The final model was a recurrent neural network with 6 features (creatinine, blood urea nitrogen, urine specific gravity, urine protein, weight, age). Identifying CKD at the time of diagnosis, the model displayed a sensitivity of 91.4% and a specificity of 97.2%. When predicting future risk of CKD, model sensitivity was 68.8% at 1 year, and 44.8% 2 years before diagnosis. Positive predictive value (PPV) varied between 15 and 23% and was influenced by the age of the patient, while the negative predictive value remained above 99% under all tested conditions. While the modest PPV limits its use as a stand-alone diagnostic screening tool, high specificity and NPV make the model particularly effective at identifying patients that will not go on to develop CKD.

Dietary calcium to phosphorus ratio affects postprandial phosphorus concentrations in feline plasma.

The impact of dietary phosphorus on chronic renal disease in cats, humans and other species is receiving increasing attention. As Ca and P metabolism are linked, the ratio of Ca:P is an important factor for consideration when formulating diets for cats and other animals. Here, we describe a fully randomised crossover study including twenty-four healthy, neutered adult cats, investigating postprandial responses in plasma P, ionised Ca and parathyroid hormone (PTH) following one meal (50 % of individual metabolic energy requirement) of each of six experimental diets. Diets were formulated to provide P at either 0·75 or 1·5 g/1000 kcal (4184 kJ) from the soluble phosphorus salt sodium tripolyphosphate (STPP, Na5P3O10), variable levels of organic Ca and P sources, and an intended total Ca:P of about 1·0, 1·5 or 2·0. For each experimental diet, baseline fasted blood samples were collected prior to the meal, and serial blood samples collected hourly for 6 h thereafter. For all diets, a significant increase from baseline was observed at 120 min in plasma PTH (P < 0·001). The diet containing the highest STPP inclusion level and lowest Ca:P induced the highest peaks in postprandial plasma P and PTH levels (1·8 mmol/l and 27·2 pg/ml, respectively), and the longest duration of concentrations raised above baseline were observed at 3 h for P and 6 h for PTH. Data indicate that Ca:P modulates postprandial plasma P and PTH. Therefore, when formulating diets containing soluble P salts for cats, increasing the Ca:P ratio should be considered.

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.

Healthy Ageing Is Associated with Preserved or Enhanced Nutrient and Mineral Apparent Digestibility in Dogs and Cats Fed Commercially Relevant Extruded Diets.

Age-related changes in gastrointestinal function have been reported in companion animals, but the impact on digestive efficiency remains uncertain. Healthy dogs (n = 37; 2.6-14.2 years) received four diets varying in total dietary fibre (TDF; 6-29%, as fed). Healthy cats (n = 28; 1-13 years) received four diets with two fat (10-12%; 17-18%) and TDF (9 and 12%) levels. In a crossover design, diets were provided over four consecutive 10-day cycles, including a 4-day faecal collection. Apparent crude protein (CP), ether extract (EE), TDF, calcium (Ca), and phosphorus (P) digestibilities were determined. The effect of age was analysed as a continuous variable in dogs and as differences between adult (1-5 years) and senior (7-13 years) cats. In dogs, EE digestibility was unaffected by age (p > 0.10). Dogs of 6-12 years had higher digestibility of CP (p = 0.032), TDF (p = 0.019), Ca (p = 0.019), and P (p = 0.024) when fed the 6% TDF diet. Senior cats had greater digestibility of TDF (p < 0.01) and Ca (p = 0.024) but had lower EE and CP digestibility with one diet (17% fat; 9%TDF) (age, p > 0.10; diet × age, p < 0.001). Healthy ageing was associated with preserved nutrient digestibility in dogs and cats within the age ranges studied. The effect of ingredient sources in senior cats warrants further investigation.

Adaptations Supporting Plasma Methionine on a Limited-Methionine, High-Cystine Diet Alter the Canine Plasma Metabolome Consistent with Interventions that Extend Life Span in Other Species.

BACKGROUND: Using indicator amino acid oxidation methodology, the mean dietary requirement of adult dogs for methionine (Met) was estimated to be ∼66% of the current recommended allowance. Dogs fed a diet formulated to provide the estimated mean Met requirement for 32 wk maintained plasma Met, seemingly supported by betaine oxidation. OBJECTIVE: To gain a better understanding of the metabolic changes that were associated with supporting plasma Met when dogs were fed a limited Met diet over 32 wk, we analyzed plasma samples taken from that study using a data-driven metabolomics approach. METHODS: Labrador retrievers (20 females/13 males; mean age: 4.9 y; range: 2.0-7.9 y) were fed semi-purified, nutritionally complete diets. After 4 wk of feeding a control diet (DL-Met; 1.37 g/1000 kcal), 17 dogs remained on this diet and 16 were transitioned to a test diet formulated to the estimated mean Met requirement (0.55 g/1000 kcal), with dietary total sulfur amino acid maintained with additional l-cystine (Cys). Dogs were individually fed diets to maintain a stable body weight at an ideal body condition score for 32 wk. Plasma samples from fasted blood collected at baseline and 8 and 32 wk were analyzed using untargeted metabolic profiling. RESULTS: Analysis of metabolites (n = 593) confirmed our primary findings (increased Met, betaine, and dimethylglycine). Metabolite changes consistent with repartitioning choline to support Met cycling included reduced pools of lipids derived via phosphatidylethanolamine N-methyltransferase and enhanced fatty acid oxidation. Some changes were consistent with metabolomics studies reported in other species that used interventions known to extend life span (caloric- and Met-restricted diets or feeding strategy). CONCLUSIONS: Changes in the plasma metabolome were consistent with reported adaptations to support Met-dependent activities. We propose that feeding a limited-Met, high-Cys diet using the estimated mean Met requirement in adult Labrador retrievers alters regulation of the Met cycle, thereby altering metabolism, similar to interventions that extend life span.

No Observed Adverse Effects on Health Were Detected in Adult Beagle Dogs When Fed a High-Calcium Diet for 40 Weeks.

The implications of long-term high calcium (Ca) intake are well documented in growing dogs and in adult dogs of large breed size, however, the consequences on other breeds and breed sizes are yet to be determined. Eighteen neutered adult beagles, nine males and nine females aged 1.4-4.4 years, were randomized to control or test diets providing in g∙4184 kJ-1 (1000 kcal-1): 1.44 and 7.19 total Ca balanced with 1.05 and 4.25 total phosphorus, respectively, for 40 weeks. Health parameters, ultrasound scans, radiographs, glomerular filtration rate, and mineral balance were measured at eight-week intervals. All dogs remained healthy with no measured evidence of orthopedic, urinary, or renal disease. The test diet resulted in a 5.2 fold increase in fecal Ca excretion. Apparent Ca digestibility (%) and Ca balance (g/d) did not significantly (p > 0.05) change from baseline in the test diet group, although dogs displayed a positive Ca balance (maximum at week 8, 1.11 g/d with 95% CI (0.41, 1.80)) before a neutral Ca balance was restored at week 32. Despite an initial positive Ca balance, we can conclude that no measurable adverse health effects were observed as a result of the test diet fed in this study in beagles over a period of 40 weeks.

Energy Requirements for Growth in the Norfolk Terrier.

An appropriate energy intake for healthy growth can reduce the risk of obesity and co-morbidities, such as orthopaedic diseases. The 2006 National Research Council (NRC) universal equation calculates the energy requirement of growing dogs based on predicted adult body weight, but evidence suggests a revision may be required. This study investigates the energy requirements of seventeen Norfolk terrier puppies over their first year (10 to 52 weeks). Puppies were individually fed complete and balanced diets in amounts to maintain an optimal body condition score (BCS), recording intake daily and body weight and BCS weekly. To monitor health a veterinary examination, haematology and plasma biochemistry and serum measures of bone turnover were undertaken every 12 weeks. Skeletal development was assessed using dual-energy X-ray absorptiometry (26 and 52 weeks). Puppies were clinically healthy with normal skeletal development and healthy growth throughout. The energy intake to achieve this was significantly lower than that predicted by the NRC (2006) equation at all time points, with largest mean difference of 285 kJ/kg0.75 per day at 10 weeks. If fed according to the NRC 2006 equation, dogs would have been in positive energy balance, possibly leading to obesity. These data support a revision to the NRC (2006) equation.

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.

High-throughput glycomic analyses reveal unique oligosaccharide profiles of canine and feline milk samples.

Oligosaccharides are important components of milk, serving as substrates for the intestinal microbiota, acting as antimicrobials that prevent pathogen colonization, and supporting the developing gastrointestinal immune system of neonates. Nutrient composition of canine and feline milk samples has been described previously, but little is known about the oligosaccharide content. Therefore, the objective of this study was to characterize canine and feline milk samples using a high-throughput glycomics approach. 23 dogs (9 Labrador retriever and 14 Labrador retriever x golden retriever crossbreed) and 6 domestic shorthair cats were recruited to the study. Milk samples were collected by manual expression at time points after parturition. Samples were collected across 2 phases per species, differentiated by maternal diet. Following extraction, oligosaccharide content was determined by liquid chromatography-mass spectrometry (LC-MS). In canine milk samples, 3 structures accounted for over 90% of all oligosaccharides detected across two diet groups. These were 3'-sialyllactose, 6'-sialyllactose, and 2'-fucosyllactose. In feline samples, a more diverse range of oligosaccharides was detected, with up to 16 structures present at relative abundance >1% of the total. Difucosyllactose-N-hexaose b, 3'-sialyllactose and lacto-N-neohexaose were all detected at abundances >10% in feline milk samples. Statistically significant differences (p<0.05) in oligosaccharide abundances were observed between collection time points and between diet groups within species. These data explore the oligosaccharide content of canine and feline maternal milk, representing an opportunity to generate a fundamental understanding of the nutritional needs of new-born puppies and kittens.

Predicting early risk of chronic kidney disease in cats using routine clinical laboratory tests and machine learning.

BACKGROUND: Advanced machine learning methods combined with large sets of health screening data provide opportunities for diagnostic value in human and veterinary medicine. HYPOTHESIS/OBJECTIVES: To derive a model to predict the risk of cats developing chronic kidney disease (CKD) using data from electronic health records (EHRs) collected during routine veterinary practice. ANIMALS: A total of 106 251 cats that attended Banfield Pet Hospitals between January 1, 1995, and December 31, 2017. METHODS: Longitudinal EHRs from Banfield Pet Hospitals were extracted and randomly split into 2 parts. The first 67% of the data were used to build a prediction model, which included feature selection and identification of the optimal neural network type and architecture. The remaining unseen EHRs were used to evaluate the model performance. RESULTS: The final model was a recurrent neural network (RNN) with 4 features (creatinine, blood urea nitrogen, urine specific gravity, and age). When predicting CKD near the point of diagnosis, the model displayed a sensitivity of 90.7% and a specificity of 98.9%. Model sensitivity decreased when predicting the risk of CKD with a longer horizon, having 63.0% sensitivity 1 year before diagnosis and 44.2% 2 years before diagnosis, but with specificity remaining around 99%. CONCLUSIONS AND CLINICAL IMPORTANCE: The use of models based on machine learning can support veterinary decision making by improving early identification of CKD.

Metabolomic profiling to identify effects of dietary calcium reveal the influence of the individual and postprandial dynamics on the canine plasma metabolome.

Short-term feeding studies have highlighted a phenomenon in Ca regulation that raises concerns around Ca absorption in dogs that may make an impact on commercial diets near to the maximum recommended level. A recent study to determine responses in dogs fed one of two diets differing in dietary Ca over 40 weeks found no evidence to suggest a concern across a range of biological parameters hypothesised to be affected by Ca. Unforeseen consequences of dietary Ca could have occurred and metabolic profiling was deemed a suitable data-driven approach to identify effects of dietary Ca. The objectives were to compare the fasted plasma metabolome (sampled at 8-week intervals over 40 weeks) of dogs fed one of two diets, near to the minimum and maximum recommended levels of dietary Ca. Comparisons with the control diet were also investigated across the postprandial time course (1-4 h) following acute (1 d) and long-term (24 weeks) feeding of the test diet. Comparing fasted plasma samples at each time point, no significant effect (adjusted P < 0·05) of diet on metabolites was observed. In the postprandial state, only phosphate was consistently different between diets and was explained by additional dietary P to maintain Ca:P. Metabolic profiling analysis supports the view that the dietary Ca upper limit is safe. Additionally, the canine plasma metabolome was characterised, providing insights into the stability of individual profiles across 40 weeks, the response to consumption of a nutritionally complete meal over a 4 h postprandial time course and different kinetic categories of postprandial absorption.

Not all forms of dietary phosphorus are equal: an evaluation of postprandial phosphorus concentrations in the plasma of the cat.

Phosphorus is present in diets as naturally occurring P from raw materials or added as an inorganic salt. However, little is known about postprandial kinetics of P absorption in cats. Here, we describe several studies quantifying postprandial kinetics following the ingestion of diets of varying composition. Briefly, cats were fed a meal consisting of 50 % of their metabolic energy requirement in a randomised crossover design. A pre-meal baseline blood sample was taken via cephalic catheter and repeated measurements taken regularly up to 6 h post-meal to assess the whole blood ionised Ca, plasma P and parathyroid hormone concentrations. A diet containing 4·8 g total P/4184 kJ (1000 kcal), 3·5 g P from sodium dihydrogen phosphate (NaH2PO4)/4184 kJ (1000 kcal) and Ca:P 0·6 caused a marked increase in plasma P from baseline to a peak of 1·976 (95% CI 1·724, 2·266) mmol/l (P <0·001), whereas a diet containing 3·38 g total P/4184 kJ (1000 kcal), no added inorganic P and Ca:P 1·55 resulted in a postprandial decrease in plasma P (P = 0·008). Subsequent data indicate that added inorganic P salts in the diet above 0·5 g P/4184 kJ (1000 kcal) cause an increase in plasma P in cats, while diets below this do not. The data presented here demonstrate that sources of added inorganic P salts cause a temporary postprandial increase in plasma P in a dose-dependent manner, prolonged in diets with Ca:P <1·0. Dietary P derived from natural food ingredients (e.g. meat or vegetable matter) does not appear to have any effect on postprandial plasma P.

Effects of the long-term feeding of diets enriched with inorganic phosphorus on the adult feline kidney and phosphorus metabolism.

Renal disease has a high incidence in cats, and some evidence implicates dietary P as well. To investigate this further, two studies in healthy adult cats were conducted. Study 1 (36 weeks) included forty-eight cats, stratified to control or test diets providing 1·2 or 4·8 g/1000 kcal (4184 kJ) P (0 or approximately 3·6 g/1000 kcal (4184 kJ) inorganic P, Ca:P 1·2, 0·6). Study 2 (29 weeks) included fifty cats, stratified to control or test diets, providing 1·3 or 3·6 g/1000 kcal (4184 kJ) P (0 or approximately 1·5 g/1000 kcal (4184 kJ) inorganic P, Ca:P 1·2, 0·9). Health markers, glomerular filtration rate (GFR) and mineral balance were measured regularly, with abdominal ultrasound. Study 1 was halted after 4 weeks as the test group GFR reduced by 0·4 (95 % CI 0·3, 0·5) ml/min per kg, and ultrasound revealed changes in renal echogenicity. In study 2, at week 28, no change in mean GFR was observed (P >0·05); however, altered renal echogenicity was detected in 36 % of test cats. In agreement with previous studies, feeding a diet with Ca:P <1·0, a high total and inorganic P inclusion resulted in loss of renal function and changes in echogenicity suggestive of renal pathology. Feeding a diet containing lower total and inorganic P with Ca:P close to 1·0 led to more subtle structural changes in a third of test cats; however, nephrolithiasis occurred in both diet groups, complicating data interpretation. We conclude that the no observed adverse effects level for total dietary P in adult cats is lower than 3·6 g/1000 kcal (4184 kJ), however the effect of inorganic P sources and Ca:P require further investigation.