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1.
Vet J ; 306: 106181, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38897377

ABSTRACT

Chronic kidney disease (CKD) in cats and dogs presents significant clinical challenges, with emerging research highlighting the pivotal role of the gut-kidney axis in its pathogenesis and management. Gut dysbiosis, characterized by alterations in the gut microbiome composition and function, contributes to microbial dysmetabolism of key nutrients causing uremic toxin accumulation and disruptions in amino acid, bile acid and fatty acid profiles. These disturbances in turn exacerbate renal dysfunction and systemic inflammation. Recent research in veterinary medicine, particularly in cats, supports the gut microbiome and microbial-derived metabolites as novel therapeutic targets. Potential therapeutic strategies targeting the gut microbiome and microbial dysmetabolism, including dietary management, probiotics, adsorbents, and addressing constipation, offer promising avenues for intervention to restore metabolic balance and preserve renal function. This review highlights the microbial influence on renal health and focuses on potential therapeutic strategies available to veterinarians to optimize the management of CKD in cats and dogs.

2.
J Feline Med Surg ; 26(5): 1098612X241240326, 2024 May.
Article in English | MEDLINE | ID: mdl-38770706

ABSTRACT

OBJECTIVES: The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD). METHODS: A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location. RESULTS: After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; P = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; P = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; P = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups). CONCLUSIONS AND RELEVANCE: Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.


Subject(s)
Blood Pressure , Cat Diseases , Cross-Over Studies , Gabapentin , Renal Insufficiency, Chronic , Animals , Cats , Gabapentin/administration & dosage , Gabapentin/pharmacology , Gabapentin/therapeutic use , Cat Diseases/drug therapy , Renal Insufficiency, Chronic/veterinary , Renal Insufficiency, Chronic/drug therapy , Blood Pressure/drug effects , Male , Female
3.
Vet Sci ; 11(3)2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38535846

ABSTRACT

The purpose of this study was to evaluate plasma ondansetron (OND) concentrations in a population of dogs with naturally occurring nausea after oral OND administration. Twenty-four dogs were randomly assigned to receive one of the following doses of oral OND: 0.5 mg/kg q8h, 0.5 mg/kg q12h, 1 mg/kg q8h, or 1 mg/kg q12h. Blood samples for plasma OND measurements were collected at baseline and 2, 4, and 8 h after administration of the first dose of OND. OND concentrations averaged over an 8 h time period were not significantly different between dose groups (0.5 mg/kg group: median 8.5 ng/mL [range 1-96.8 ng/mL], 1 mg/kg group: median 7.4 ng/mL [range 1-278.7 ng/mL]). The mean maximum concentrations in the 0.5 mg/kg and 1 mg/kg groups were 35.8 ± 49.0 ng/mL and 63.3 ± 121.1 ng/mL, respectively. OND concentrations were below the lower limit of quantification (LLOQ) in 50% (18/36) of samples in the 0.5 mg/kg groups and 39% (14/36) of samples in the 1 mg/kg groups. Six dogs (6/24, 25%) did not have OND detected at any time. The mean nausea scores at baseline were similar amongst all groups and decreased over time. The bioavailability of oral OND appears to be poor. Despite low plasma OND concentrations, nausea scores improved over time.

4.
Sci Rep ; 14(1): 4755, 2024 02 27.
Article in English | MEDLINE | ID: mdl-38413739

ABSTRACT

Evaluation of the metabolome could discover novel biomarkers of disease. To date, characterization of the serum metabolome of client-owned cats with chronic kidney disease (CKD), which shares numerous pathophysiological similarities to human CKD, has not been reported. CKD is a leading cause of feline morbidity and mortality, which can be lessened with early detection and appropriate treatment. Consequently, there is an urgent need for early-CKD biomarkers. The goal of this cross-sectional, prospective study was to characterize the global, non-targeted serum metabolome of cats with early versus late-stage CKD compared to healthy cats. Analysis revealed distinct separation of the serum metabolome between healthy cats, early-stage and late-stage CKD. Differentially abundant lipid and amino acid metabolites were the primary contributors to these differences and included metabolites central to the metabolism of fatty acids, essential amino acids and uremic toxins. Correlation of multiple lipid and amino acid metabolites with clinical metadata important to CKD monitoring and patient treatment (e.g. creatinine, muscle condition score) further illustrates the relevance of exploring these metabolite classes further for their capacity to serve as biomarkers of early CKD detection in both feline and human populations.


Subject(s)
Cat Diseases , Renal Insufficiency, Chronic , Humans , Cats , Animals , Prospective Studies , Cross-Sectional Studies , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/veterinary , Renal Insufficiency, Chronic/metabolism , Fatty Acids , Biomarkers , Amino Acids , Cat Diseases/diagnosis
5.
J Feline Med Surg ; 25(9): 1098612X231197084, 2023 09.
Article in English | MEDLINE | ID: mdl-37751181

ABSTRACT

OBJECTIVES: The aim of the present study was to determine whether the use of headphones to eliminate audible static during Doppler ultrasonic sphygmomanometry affects blood pressure (BP) measurement in conscious young adult (aged 1-6 years) and mature adult/senior (aged ⩾7 years) cats. METHODS: A randomized crossover study was conducted. Healthy client-owned cats (>1 year) were enrolled. Blood pressure measurements were obtained twice, 14 days apart, with or without the use of headphones worn by a veterinarian. A fear, anxiety and stress (FAS) score (0 = relaxed; 4 = severe signs) was recorded. A linear mixed-effects model was used to compare the effect of wearing headphones on BP measurement. RESULTS: In total, 18 young adult and 14 mature adult and senior cats with a median age of 5 years (range 1-14 years) were enrolled. Of the cats, 47% (15/32) had an average BP measurement that was at least 10 mmHg higher when using headphones compared with when not using headphones, of which a majority (11/15, 73%) were young adult cats. The average BP measurement was not different when using headphones compared with when not using headphones (mean difference -7 mmHg; 95% confidence interval -14 to 0.6; P = 0.07). When compared within age groups, the average BP measurement taken when using headphones (125 ± 15 mmHg) was lower compared with the measurement taken when not using headphones (137 ± 17 mmHg) in young adult cats (P = 0.02). CONCLUSIONS AND RELEVANCE: The reduction in the average BP measurement with the use of headphones suggests this method may be helpful in reducing situational hypertension, particularly in young adult cats. Our findings also highlight the importance of consistent use of headphones when comparing serial measurements in a cat.


Subject(s)
Cat Diseases , Hypertension , Cats , Animals , Ultrasonics , Blood Pressure , Cross-Over Studies , Blood Pressure Determination , Hypertension/veterinary
6.
Vet Sci ; 10(8)2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37624284

ABSTRACT

The purpose of this study was to evaluate the effect of feeding healthy adult cats with foods containing variable protein concentrations on the fecal microbiome and serum concentrations of the gut-derived uremic toxins indoxyl sulfate, p-cresol sulfate (pCS), and trimethylamine-n-oxide. Twenty healthy young adult cats were randomized into two groups and fed either a low-protein diet (LPD; 7.4 g/100 kcal ME) or a high-protein diet (HPD; 11.0 g/100 kcal ME) for a 12-week period. Serum uremic toxin concentrations were measured via liquid chromatography tandem mass spectrometry, and the fecal microbiome was characterized using shallow sequence shotgun metagenomics. Cats that consumed the HPD had higher pCS concentrations at 8 weeks (p = 0.028) when compared to baseline. After 12 weeks, cats fed the HPD had higher fecal alpha diversity indices at both the taxonomic and functional levels and lower fecal Bifidobacterium relative abundance compared to those cats fed the LPD. In conclusion, a change in diet and dietary protein concentration shifted the fecal microbial community and microbial function. Feeding cats a high amount of protein increased serum concentrations of the uremic toxin pCS; however, the effect was short-lived.

7.
Vet Sci ; 10(7)2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37505868

ABSTRACT

Appetite abnormalities and weight loss are important comorbidities in the treatment of chronic kidney disease (CKD) in cats. Ghrelin, a key hormone involved in the regulation of appetite and metabolism, is a potential marker of appetite dysregulation in cats with CKD. The aim of this study was to compare the plasma concentrations of acylated, desacyl, and total ghrelin in normal cats and cats with CKD. Storage methodology was investigated prior to evaluating ghrelin concentrations in normal and CKD cats to facilitate clinical sample collection. Twelve normal cats and twelve cats with CKD were enrolled. Plasma acylated and total ghrelin concentrations were measured using radioimmunoassay. Desacyl ghrelin was calculated (total ghrelin minus acylated ghrelin). Cats with CKD had significantly increased total ghrelin and calculated desacyl ghrelin concentrations in comparison to normal cats (p < 0.0001 and p = 0.0001). There was no significant difference in active ghrelin concentrations between groups. Both total ghrelin and calculated desacyl ghrelin were significantly correlated with serum creatinine concentrations (p < 0.0001, r = 0.70 and p < 0.0001, r = 0.73). Elevated plasma desacyl ghrelin concentrations in cats with CKD provides evidence for dysregulation of appetite in feline CKD.

8.
J Vet Diagn Invest ; 35(3): 246-251, 2023 May.
Article in English | MEDLINE | ID: mdl-36896661

ABSTRACT

Measuring 25-hydroxyvitamin D (25D) can be a challenge in veterinary medicine because of laboratory accessibility and required sample volume. We compared 2 dried-blood-spot (DBS) tests and a lateral flow assay (LFA) to the gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS). We hypothesized that there would be good agreement among the tests, within a clinically significant limit of agreement of ± 25 nmol/L. We collected blood from 6 healthy purpose-bred 2-y-old cats at 6 times over 6 wk, and measured 25D concentrations with all 4 tests. Agreement of the 3 candidate tests and LC-MS/MS was evaluated via Bland-Altman analysis, Passing-Bablok regression, and Lin correlation coefficients. Bland-Altman analysis demonstrated that the mean bias was >± 25 nmol/L for all 3 candidate tests in comparison to serum LC-MS/MS concentrations. The 95% CIs for the mean bias did not include zero, further supporting the presence of significant bias among methods. Additionally, all 3 tests had poor agreement with serum LC-MS/MS concentrations when analyzed by Lin correlation coefficient analysis, and bias between methods was further characterized by Passing-Bablok analysis. Based on these results, none of these 3 tests is recommended as an alternative to LC-MS/MS testing for 25D measurement in cats.


Subject(s)
Tandem Mass Spectrometry , Vitamin D , Cats , Animals , Chromatography, Liquid/veterinary , Chromatography, Liquid/methods , Tandem Mass Spectrometry/veterinary , Vitamin D/analysis , Serum/chemistry
9.
Front Vet Sci ; 10: 1039931, 2023.
Article in English | MEDLINE | ID: mdl-36846255

ABSTRACT

Fecal diagnostics are a mainstay of feline medicine, and fecal identification markers help to distinguish individuals in a multi-cat environment. However, the impact of identification markers on the fecal microbiota are unknown. Given the increased interest in using microbiota endpoints to inform diagnosis and treatment, the objective of this study was to examine the effects of orally supplemented glitter and crayon shavings on the feline fecal microbiota (amplicon sequencing of 16S rRNA gene V4 region). Fecal samples were collected daily from six adult cats that were randomized to receive oral supplementation with either glitter or crayon for two weeks, with a two-week washout before receiving the second marker. No adverse effects in response to marker supplementation were seen for any cat, and both markers were readily identifiable in the feces. Microbiota analysis revealed idiosyncratic responses to fecal markers, where changes in community structure in response to glitter or crayon could not be readily discerned. Given these findings, it is not recommended to administered glitter or crayon shavings as a fecal marker when microbiome endpoints are used, however their clinical use with other diagnostics should still be considered.

10.
J Vet Intern Med ; 37(2): 556-566, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36807589

ABSTRACT

BACKGROUND: Hypoxia is a key driver of fibrosis and is associated with capillary rarefaction in humans. OBJECTIVES: Characterize capillary rarefaction in cats with chronic kidney disease (CKD). ANIMALS: Archival kidney tissue from 58 cats with CKD, 20 unaffected cats. METHODS: Cross-sectional study of paraffin-embedded kidney tissue utilizing CD31 immunohistochemistry to highlight vascular structures. Consecutive high-power fields from the cortex (10) and corticomedullary junction (5) were digitally photographed. An observer counted and colored the capillary area. Image analysis was used to determine the capillary number, average capillary size, and average percent capillary area in the cortex and corticomedullary junction. Histologic scoring was performed by a pathologist masked to clinical data. RESULTS: Percent capillary area (cortex) was significantly lower in CKD (median 3.2, range, 0.8-5.6) compared to unaffected cats (4.4, 1.8-7.0; P = <.001) and was negatively correlated with serum creatinine concentrations (r = -.36, P = .0013), glomerulosclerosis (r = -0.39, P = <.001), inflammation (r = -.30, P = .009), and fibrosis (r = -.30, P = .007). Capillary size (cortex) was significantly lower in CKD cats (2591 pixels, 1184-7289) compared to unaffected cats (4523 pixels, 1801-7618; P = <.001) and was negatively correlated with serum creatinine concentrations (r = -.40, P = <.001), glomerulosclerosis (r = -.44, P < .001), inflammation (r = -.42, P = <.001), and fibrosis (r = -.38, P = <.001). CONCLUSIONS AND CLINICAL IMPORTANCE: Capillary rarefaction (decrease in capillary size and percent capillary area) is present in kidneys of cats with CKD and is positively correlated with renal dysfunction and histopathologic lesions.


Subject(s)
Cat Diseases , Microvascular Rarefaction , Renal Insufficiency, Chronic , Humans , Cats , Animals , Microvascular Rarefaction/complications , Microvascular Rarefaction/pathology , Microvascular Rarefaction/veterinary , Cross-Sectional Studies , Creatinine , Kidney/pathology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/veterinary , Fibrosis , Inflammation/pathology , Inflammation/veterinary , Cat Diseases/pathology
11.
J Feline Med Surg ; 24(12): e472-e480, 2022 12.
Article in English | MEDLINE | ID: mdl-36475921

ABSTRACT

OBJECTIVES: In humans, renal aging is associated with an increased frequency of glomerulosclerosis, interstitial fibrosis, inflammation and tubular atrophy. The purpose of this study was to describe the frequency of renal histopathologic lesions in cats without kidney disease. METHODS: A cross-sectional study of archival kidney tissue from 74 cats without kidney disease (serum creatinine <1.6 mg/dl; urine specific gravity >1.035) was carried out: 0-4 years (young, n = 18); 5-9 years (mature, n = 16); 10-14 years (senior, n = 34), 15+ years (geriatric, n = 6). Glomerulosclerosis, tubular atrophy, interstitial inflammation and fibrosis, and the presence or absence of lipid in the interstitium and tubules were scored by a pathologist masked to clinical data. Statistical analyses were performed as appropriate. RESULTS: Geriatric cats had significantly more glomerulosclerosis than mature (P = 0.01) and young cats (P = 0.004). Senior cats had significantly more glomerulosclerosis than young cats (P = 0.006). Glomerulosclerosis was weakly positively correlated with age (r = 0.48; P <0.0001). Geriatric cats had significantly more tubular atrophy than mature (P = 0.02) and young cats (P <0.0001). Senior cats had significantly more tubular atrophy than young cats (P <0.0001). Geriatric cats had significantly more inflammation than senior cats (P = 0.02), mature cats (P = 0.01) and young cats (P <0.0001). Senior cats had significantly more inflammation than young cats (P = 0.004). Geriatric and senior cats had significantly more fibrosis than young cats (P = 0.01 and P = 0.04, respectively). Frequency of tubular lipid increased with age (young: 28%; mature: 56%; senior: 79%; geriatric: 100%) as did the frequency of interstitial lipid (young: 22%, mature: 56%, senior: 85%, geriatric: 100%). CONCLUSIONS AND RELEVANCE: Evidence of renal aging exists in cats. These changes imply that the aging kidney may be more susceptible to injury and impaired healing.


Subject(s)
Cat Diseases , Kidney Diseases , Humans , Cats , Animals , Cross-Sectional Studies , Kidney Diseases/epidemiology , Kidney Diseases/veterinary , Kidney , Fibrosis , Atrophy/veterinary , Lipids , Cat Diseases/epidemiology
12.
J Feline Med Surg ; 24(12): e459-e464, 2022 12.
Article in English | MEDLINE | ID: mdl-36219454

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the magnitude, duration and significance of postprandial changes to select serum biochemistry analytes in healthy adult cats in the 12 h period after a meal. METHODS: Nine adult research cats fed commercial food were included. Blood samples were taken after a 12 h fast (hour 0), cats were offered and consumed a meal, and postprandial samples were obtained over a 12 h period starting 2 h after the baseline blood draw (hours 2, 4, 6, 8, 10 and 12). Serum samples were run on a Roche Cobas C501 chemistry analyzer to obtain concentrations of blood urea nitrogen (BUN), creatinine, phosphorus, total calcium, bicarbonate, cholesterol, magnesium, sodium, potassium and chloride. Serum concentrations of each analyte at hours 2, 4, 6, 8, 10 and 12 were compared with concentrations prior to feeding. RESULTS: Serum concentration for at least one postprandial time point was different from baseline fasted concentration for BUN (hour 2, P = 0.006; hour 4, P <0.0001; hour 6, P = 0.002; hour 8, P = 0.026), phosphorus (hour 2, P = 0.019), bicarbonate (hours 2, 4, 6, 8 and 10; all P <0.01), glucose (hour 12, P = 0.014), magnesium (hour 10, P = 0.029) and chloride (hour 2, P = 0.026; hour 4, P = 0.044; hour 12, P = 0.019). No significant difference was seen at any postprandial sampling point compared with baseline for serum creatinine, total calcium, cholesterol, sodium or potassium concentrations. CONCLUSIONS AND RELEVANCE: Short-term postprandial serum concentrations of BUN, phosphorus, bicarbonate and chloride differed at multiple time points within a 12 h period compared with the fasted state at baseline, with most values remaining within the reference intervals. Veterinarians should be aware of these alterations, though they are unlikely to be mistaken for pathological disease states in healthy adult cats.


Subject(s)
Bicarbonates , Chlorides , Cats , Animals , Magnesium , Calcium , Sodium , Potassium
13.
Am J Vet Res ; 83(7)2022 May 21.
Article in English | MEDLINE | ID: mdl-35930783

ABSTRACT

OBJECTIVE: To assess whether hyperinoculation of cats with a feline herpesvirus-1, calicivirus, and panleukopenia virus (FVRCP) vaccine could be used as a model to study interstitial nephritis and to assess humoral and cell-mediated immune responses toward vaccinal α-enolase. ANIMALS: 6 healthy young adult purpose-bred research cats. PROCEDURES: Baseline renal cortical biopsies, whole blood, serum, and urine were collected prior to administration of a commercial FVRCP parenteral vaccine. Vaccine hyperinoculation was defined as a total of 8 vaccinations given at 2-week intervals over a 14-week period. Blood samples were collected immediately prior to each vaccination, and a second renal biopsy was performed 2 weeks after hyperinoculation (week 16). Renal histopathology, renal α-enolase immunohistochemistry, and assays to detect humoral and cell-mediated immune reactions against Crandell-Rees feline kidney (CRFK) cell lysates and α-enolase were performed. An α-enolase immunoreactivity score for renal tubules and glomeruli based on signal intensity was determined by a blinded pathologist. RESULTS: Hyperinoculation with the vaccine was not associated with clinicopathologic evidence of renal dysfunction, and interstitial nephritis was not recognized by light microscopy in the time studied. The mean serum absorbance values for antibodies against CRFK antigen and α-enolase were significantly (P < 0.001) higher at weeks 4, 8, and 16 versus week 0. Renal tubular and glomerular α-enolase immunoreactivity scores were higher at week 16 compared to baseline. CLINICAL RELEVANCE: Findings suggested that systemic immunological reactions occurred and renal tissues were affected by vaccine hyperinoculation; however, short-term FVRCP vaccine hyperinoculation cannot be used to study interstitial nephritis in cats.


Subject(s)
Calicivirus, Feline , Cat Diseases , Herpesviridae , Viral Vaccines , Animals , Antibodies, Viral , Cat Diseases/pathology , Cat Diseases/prevention & control , Cats , Feline Panleukopenia Virus , Kidney , Phosphopyruvate Hydratase , Varicellovirus
14.
Am J Vet Res ; 83(7)2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35930788

ABSTRACT

OBJECTIVE: To characterize uropathogenic Escherichia coli (UPEC) in cases of clinical feline urinary tract infection (UTI) and subclinical bacteriuria and investigate the in vitro effects of E coli strain Nissle 1917 on isolate growth. ANIMALS: 40 cats with positive E coli culture results for urine collected during routine evaluation. PROCEDURES: Characterization of UPEC isolates was performed by PCR-based phylotype analysis and serotyping. Nissle 1917 effects on growth inhibition and competitive overgrowth against UPEC isolates were evaluated in vitro using a plate-based competition assay. RESULTS: Feline phylogroups were similar to previous human and feline UPEC studies, with most of the isolates belonging to phylogroup A (42.5%), B2 (37.5%), and D (15.0%). Fifty-two percent of isolates were found to be resistant to antimicrobials, with 19% of these being multidrug resistant (MDR). Nissle 1917 adversely affected the growth of 82.5% of all isolates and 100% of MDR isolates in vitro. The median zone of inhibition was 3.33 mm (range, 1.67 to 10.67 mm). Thirteen isolates were affected via competitive overgrowth and 20 via growth inhibition. CLINICAL RELEVANCE: UPEC isolates from cats were similar in phylogroup analysis to human and dog isolates. The in vitro effects of Nissle 1917 on UPEC warrant additional studies to determine if similar results can be duplicated in vivo.


Subject(s)
Cat Diseases , Escherichia coli Infections , Probiotics , Urinary Tract Infections , Uropathogenic Escherichia coli , Animals , Cats , Escherichia coli Infections/veterinary , Humans , Phylogeny , Urinary Tract Infections/veterinary
15.
J Vet Intern Med ; 36(5): 1693-1699, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35962709

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) leads to low serum concentrations of vitamin D metabolites. Thus, hypovitaminosis D associated with CKD might contribute to disease progression via increased concentration of renin angiotensin aldosterone system (RAAS) mediators. OBJECTIVES: To evaluate whether supplementation with calcifediol affects equilibrium concentrations of selected mediators of the RAAS. We hypothesized that vitamin D supplementation will decrease concentration of circulating RAAS mediators in dogs with CKD. ANIMALS: Six client-owned adult dogs with IRIS Stage 2 and 3 CKD. METHODS: Prospective study. Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), RAAS mediators (angiotensin I/II/III/IV/1-5/1-7, and aldosterone), and surrogate angiotensin converting enzyme (ACE) activity (calculated by the ratio of angiotensin II to angiotensin I) were evaluated at baseline, after 3 months of calcifediol supplementation, and 2 months after discontinuing administration of supplement. RESULTS: All serum vitamin D metabolite concentrations increased significantly by month 3 (P < .001): 25(OH)D (median 250 ng/mL; range, 204-310), compared to baseline (median 43.2 ng/mL; range, 33.8-58.3 ng/mL); 1,25(OH)2 D (median 66.1 pg/mL; range, 57.3-88.1 pg/mL) compared to baseline (median 35.2 pg/mL; range, 29.3-56.7 pg/mL); 24,25(OH)2 D (median 68.4 ng/mL; range, 22.1-142.0 ng/mL) compared to baseline (median 14.4 ng/mL; range, 9.0-21.3 ng/mL). Calculated ACE activity was significantly lower at month 3 (median 0.5; range, 0.4-1.0) compared to baseline (median 0.7; range, 0.6-1.3; P = .01). There were no significant differences in any of the evaluated RAAS variables at any other time-point. CONCLUSIONS AND CLINICAL IMPORTANCE: Short-term calcifediol supplementation in this small group of CKD dogs appeared to decrease ACE activity.


Subject(s)
Dog Diseases , Renal Insufficiency, Chronic , Aldosterone , Angiotensin I/pharmacology , Angiotensin II , Animals , Calcifediol/pharmacology , Dietary Supplements , Dog Diseases/drug therapy , Dogs , Peptidyl-Dipeptidase A , Prospective Studies , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/veterinary , Renin-Angiotensin System , Vitamin D
16.
J Vet Pharmacol Ther ; 45(6): 508-515, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35899472

ABSTRACT

The purpose of this study was to evaluate the pharmacokinetics of intravenous (IV) ondansetron in a population of hospitalized dogs exhibiting clinical signs of nausea. The causes of nausea included pancreatitis, gastroenteritis, endocarditis, chemotherapy-induced nausea, diabetes mellitus and ketoacidosis, acute kidney injury with aspiration pneumonia, pyometra, uroabdomen, neoplasia, and hepatopathy. Twenty-four dogs were randomly assigned to one of the following IV ondansetron protocols: 1 mg/kg q12h, 0.5 mg/kg q12h, 1 mg/kg q8h, 0.5 mg/kg q8h. Serum was collected at 0, 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after the first dose, and nausea scores were recorded at multiple time points. Ondansetron and arginine vasopressin (AVP) concentrations were measured via high-performance liquid chromatography coupled to tandem mass spectrometry and ELISA, respectively. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Ondansetron displayed linear pharmacokinetics. In the 0.5 mg/kg group, mean Cmax  = 214 ng/ml, AUC0-8h  = 463 ng/ml*h, and calculated half-life was 1.9 h. In the 1 mg/kg group, mean Cmax  = 541 ng/ml, AUC0-8h  = 1057 ng/ml*h and calculated half-life was 1.6 h. Serum ondansetron concentrations were not significantly different between dogs that required rescue anti-nausea medication (non-responders) and dogs that did not require rescue therapy (responders). In total, 83.3% of patients in the 0.5 mg/kg q8h, 0.5 mg/kg q12h, and 1 mg/kg q8h groups had improvement in nausea scores. In total, 66.7% of patients in the 1 mg/kg q12h group had improvement in nausea scores. In total, 33% of patients had resolution of nausea in the 0.5 mg/kg q8h, 1 mg/kg q8h, and 1 mg/kg q12h groups, and 16% of patients had resolution of nausea in the 0.5 mg/kg q12h group. AVP concentrations were highly variable and did not correlate with nausea scores. Nausea scores significantly decreased regardless of dosage protocol. AVP was not a reliable biomarker of nausea in this group of dogs.


Subject(s)
Antiemetics , Ondansetron , Dogs , Animals , Ondansetron/therapeutic use , Nausea/chemically induced , Nausea/drug therapy , Nausea/veterinary , Half-Life , Area Under Curve , Double-Blind Method
17.
J Feline Med Surg ; 24(7): 614-640, 2022 07.
Article in English | MEDLINE | ID: mdl-35775307

ABSTRACT

PRACTICAL RELEVANCE: Inappetence may have many origins and, as a presenting sign or observation in the hospitalised patient, is common in feline practice. Nutritional assessment of every patient is encouraged, to identify the need for, and appropriate type of, intervention indicated. The impact of malnutrition may be significant on the feline patient, perpetuating illness, delaying recovery, slowing wound healing and negatively impacting gut health and immunity. Delayed intervention may result in the cat's deterioration; hence prompt control of contributing factors such as the underlying illness, pain, nausea, ileus and stress is vital to optimise voluntary food intake. Management is multimodal, comprising reduction of stress, medications and assisted nutrition in the form of tube feeding or parenteral nutrition. Use of antiemetic, analgesic, prokinetic and appetite stimulant medications may restore appetite, but placement of feeding tubes should not be delayed. Feeding tubes are generally well tolerated and allow provision of food, water and medication with minimal stress, although clinicians must be aware of complications such as stoma site infections and refeeding syndrome. CLINICAL CHALLENGES: Cats are vulnerable to malnutrition owing to their unique metabolism and specific nutritional requirements. Moreover, their nature as a species means they are susceptible to stress in the hospital environment, which may result in reduced food intake; previous negative experiences may compound the problem. In particular, an inappropriate clinic environment and/or handling may cause or exacerbate inappetence in hospitalised patients, with negative impacts on recovery. Postponing interventions such as feeding tube placement to await improvement, owing to clinician or caregiver apprehension, may hinder recovery and worsen nutritional deficits. EVIDENCE BASE: The 2022 ISFM Consensus Guidelines on Management of the Inappetent Hospitalised Cat have been created by a panel of experts brought together by the International Society of Feline Medicine (ISFM). Information is based on the available literature, expert opinion and the panel members' experience.


Subject(s)
Cat Diseases , Malnutrition , Animals , Appetite , Appetite Stimulants , Cat Diseases/therapy , Cats , Enteral Nutrition/veterinary , Humans , Malnutrition/veterinary , Nutrition Assessment
18.
Vet Sci ; 9(2)2022 Feb 17.
Article in English | MEDLINE | ID: mdl-35202337

ABSTRACT

The purpose of the study was to quantify serum and fecal amino acids (AA) in cats with chronic kidney disease (CKD) and compare to healthy cats. Thirty-five cats with International Renal Interest Society Stage 1-4 CKD and 16 healthy mature adult and senior client-owned cats were included in this prospective cross-sectional study. Sera were analyzed for 25 AA concentrations using an ion exchange chromatography AA analyzer with post column ninhydrin derivatization. Voided fecal samples were analyzed for 22 AA concentrations using liquid chromatography with tandem mass spectrometry. CKD cats had lower serum concentrations of phenylalanine (mean difference ± standard error of the mean: 12.7 ± 4.3 µM; p = 0.03), threonine (29.6 ± 9.2 µM; p = 0.03), tryptophan (18.4 ± 5.4 µM; p = 0.005), serine (29.8 ± 12.6 µM; p = 0.03), and tyrosine (11.6 ± 3.8 µM; p = 0.01) and higher serum concentrations of aspartic acid (4.7 ± 2.0 µM; p = 0.01), ß-alanine (3.4 ± 1.2 µM; p = 0.01), citrulline (5.7 ± 1.6 µM; p = 0.01), and taurine (109.9 ± 29.6 µM; p = 0.01) when compared to healthy cats. Fecal AA concentrations did not differ between healthy cats and CKD cats. 3-Methylhistidine-to-creatinine did not differ between healthy cats with and without muscle loss. Cats with CKD IRIS Stages 1-4 have a deranged serum amino acid profile compared to healthy cats.

19.
J Feline Med Surg ; 24(12): 1195-1202, 2022 12.
Article in English | MEDLINE | ID: mdl-35109690

ABSTRACT

OBJECTIVES: This survey of small animal veterinarians endeavored to: (1) determine current methods of indirect blood pressure measurement; (2) detail techniques used to reduce situational hypertension; and (3) better understand the obstacles to performing blood pressure measurement in cats. METHODS: An online survey was produced and circulated to members of the Veterinary Information Network. A total of 733 veterinarians who saw cats in their practice and had access to at least one indirect blood pressure device completed the entirety of the survey. RESULTS: Ninety-six percent (703/733) of veterinarians who completed the survey reported measuring indirect blood pressure in cats in their practice, with veterinary technicians conducting most (600/703; 85.3%) of these measurements. Few veterinarians (30/733; 4.1%) did not measure blood pressure, with these veterinarians citing several obstacles including: difficulty interpreting results with the occurrence of fear, anxiety and stress in cats (20/30; 66.7%); difficulty performing measurements in cats (17/30; 56.7%); and technical staff being uncomfortable performing measurements (12/30; 40.0%). Most veterinarians (300/435; 69.0%) in this survey preferred an ultrasonic Doppler flow detector with sphygmomanometry, with many (272/300; 90.7%) perceiving that the results obtained with this device were more trustworthy compared with results obtained with oscillometry. Ninety percent (633/703) of veterinarians employed techniques to reduce situational hypertension in cats. Techniques perceived to be most helpful among veterinarians included: using a quiet location (454/633; 71.7%); minimizing restraint (316/633; 49.9%); performing blood pressure prior to other procedures (eg, phlebotomy, cystocentesis) (302/633; 47.7%); avoiding other animals (219/633; 34.6%); and allowing time for acclimation (167/633; 26.4%). CONCLUSIONS AND RELEVANCE: This survey study of veterinarians helps clarify obstacles to routine blood pressure measurement in conscious cats. Veterinarians reported several strategies that they felt reduced situational hypertension in cats. The data inform modifications of techniques to increase the frequency and perceived reliability of blood pressure measurement in at-risk cats.


Subject(s)
Cat Diseases , Hypertension , Cats , Animals , Blood Pressure , Cross-Sectional Studies , Reproducibility of Results , Phlebotomy/veterinary , Hypertension/veterinary
20.
J Feline Med Surg ; 24(12): 1260-1266, 2022 12.
Article in English | MEDLINE | ID: mdl-35195476

ABSTRACT

OBJECTIVES: The purpose of this study was to assess serum concentrations of gabapentin in cats with chronic kidney disease (CKD) vs clinically healthy cats. METHODS: Five healthy cats were enrolled in a pharmacokinetic study. A single 20 mg/kg dose of gabapentin was administered orally and blood was obtained at 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24 and 36 h via a jugular catheter. Serum gabapentin concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Non-compartmental pharmacokinetic analysis was performed. The same five healthy cats plus 25 cats with stable International Renal Interest Society stage 2 (n = 14) and 3 (n = 11) CKD were enrolled in a limited sampling study. Cats in both groups received a single 10 mg/kg dose of gabapentin, and serum gabapentin concentrations and compliance scores were obtained 3 and 8 h post-administration. RESULTS: Cats with CKD had significantly higher dose-normalized serum gabapentin concentrations than normal cats at 3 h (P = 0.0012 CKD vs normal 10 mg/kg; P = 0.008 CKD vs normal 20 mg/kg) and 8 h (P <0.0001 CKD vs normal 10 mg/kg; P <0.0001 CKD vs normal 20 mg/kg). Both 3 and 8 h dose-normalized serum gabapentin concentrations were significantly correlated with serum creatinine (3 h: P = 0.03, r = 0.39; 8 h: P = 0.001, r = 0.57) and symmetric dimethylarginine (3 h: P = 0.03, r = 0.41; 8 h: P = 0.007, r = 0.48). There was a significant correlation between 3 h serum gabapentin concentrations and compliance scores (P = 0.0002, r = 0.68). CONCLUSIONS AND RELEVANCE: Cats with CKD that received 10 mg/kg of gabapentin had significantly higher dose-normalized serum concentrations than normal cats that received 20 mg/kg, supporting the need to dose-reduce in this patient population.


Subject(s)
Cat Diseases , Gabapentin , Renal Insufficiency, Chronic , Animals , Cats , Cat Diseases/drug therapy , Gabapentin/blood , Gabapentin/pharmacokinetics , Health Status , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/veterinary
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