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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 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.

Background Cats with moderate to advanced chronic kidney disease (CKD) often display clinical signs such as vomiting and decreased appetite, and frequently receive omeprazole or other acid suppressants despite a lack of evidence to support their use. Hypothesis/objectives To evaluate the effect of once-daily PO omeprazole on appetite in cats with CKD. We hypothesized that omeprazole would improve subjective appetite assessments in cats with CKD. Animals Fourteen client-owned cats with International Renal Interest Society (IRIS) stage 2 or 3 CKD and hyporexia. Methods Cats were prospectively enrolled in a multi-institutional, double-blinded, randomized, crossover study to evaluate the effect of a 14-day trial of once-daily PO omeprazole (1 mg/kg) or placebo (lactose gel capsule) on vomiting frequency and appetite. A daily log was completed by the owner during all treatment and rest periods to assess appetite using a subjective, qualitative, and 5-point scoring system. Mixed model analyses of variance were performed to determine if average daily percentage food consumed or appetite score, as measured by subjective owner assessment, differed between treatments. Results Compared to placebo, a negligible but statistically significant difference in percentage of food consumed was observed between treatments (P = .04) with once-daily omeprazole treatment resulting in a 2.7% increase in food consumption compared to placebo. No significant difference, however, was found in appetite score, body weight, or serum creatinine concentration between treatments. Conclusions and clinical importance Once-daily omeprazole does not markedly increase appetite in cats with CKD and should not be used as a first-line treatment in the absence of evidence of gastrointestinal ulceration.

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.

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.

Background The effects of epidural anesthesia in dogs undergoing cystoscopy are unknown. Objective To investigate the effect of epidural analgesia on postcystoscopy pain in dogs. Animals Twenty-six dogs undergoing routine cystoscopy for lower urinary tract disease. Methods Prospective, randomized, blinded observational study. Dogs were assigned either to a treatment group that received epidural anesthesia (preservative free morphine sulfate, 0.09 mg/kg; 1% ropivacaine, 0.2 mg/kg; total volume delivered, 1 mL/4.5 kg of body weight to a maximum of 10 mL; n = 9) or to a nonepidural control group (n = 13). Vital signs were monitored for 24 hours, and sedation and pain scores, behavioral assessments, and presence or absence of complications was evaluated for 5 days postprocedure. Results All dogs tolerated the epidural without complications. Four dogs were removed from the study because of status unblinding, lack of patient cooperation, or incomplete follow-up. No significant differences were noted in postprocedural pain scores in dogs that received epidural analgesia. Significant differences in postprocedural pain scores were noted in the nonepidural control group. No significant differences were noted in vital signs, behavioral assessments, or the proportion of dogs with a 50% increase in pain scores between the epidural and nonepidural groups. Conclusions and clinical importance Epidural anesthesia was well-tolerated. Dogs not receiving the epidural had poor postprocedural pain control. A consistent benefit for the epidural vs nonepidural group could not be identified. Additional studies are required to better assess the impact and efficacy of epidural anesthesia for cystoscopic procedures.

Background Biological variation of serum indoxyl sulfate (IS), p-cresol sulfate (pCS), and trimethylamine-n-oxide (TMAO) concentrations in cats is unknown. Objectives To determine short- and medium-term biological variation, index of individuality (II), and reference change values for serum IS, pCS, and TMAO concentrations in healthy adult cats. To determine the effect of feeding on serum concentrations. Animals Twelve healthy adult cats. Methods Prospective, cohort study. Seven serum samples over a 12-hour period (short-term) and 5 serum samples over a 19-day period (medium-term) were collected. Serum concentrations of total IS, pCS, and TMAO were measured every 2 hours in a 12-hour period (hours 0-12) after a meal in 9 cats and compared to concentrations in a nonfed state. Results For IS, the II was high using short-term (1.96) and low using medium-term (0.65) biological variation estimates. Individuality was intermediate for pCS (short-term, 0.98; medium-term, 1.17) and TMAO (short-term, 1.47; medium-term, 0.83). Serum IS, pCS, and TMAO concentrations were significantly lower in a fed state compared to a nonfed state at hours 4, 6, 8, and 12; at hours 4 and 6; and at hours 2, 4, 6, 8, 10, 12, respectively. Conclusion and clinical importance Population-based reference intervals with reference to the subject-based interval can be used to monitor serum pCS and TMAO concentrations. For IS, a subject-based and a population-based reference interval is best for short-term and medium-term monitoring, respectively. To compare serial measurements, it would be prudent to collect samples at the same time of day and consistently in either a fed or nonfed state.

Objectives The aims of this study were to determine if stable chronic kidney disease (CKD) cats and uremic crisis cats have altered platelet function, and to determine the prevalence of positive fecal occult blood in CKD cats. Methods Platelet function in normal cats, clinically stable International Renal Interest Society (IRIS) stage 2–4 CKD cats and CKD cats experiencing a uremic crisis were evaluated using impedance aggregometry. Area under the curve (AUC) at 6 mins was calculated for saline, adenosine diphosphate (AUCADP) and arachidonic acid (AUCASPI). The AUC in addition to hematocrit, platelet count and mean platelet volume (MPV) were compared between groups using the Kruskal–Wallis test followed by Dunn’s post-hoc analysis. Guaiac fecal occult blood tests were performed on fecal samples and results were compared between groups using a χ2 for trend test. Results AUCADP ( P = 0.04) and AUCASPI ( P = 0.05) were significantly higher in uremic crisis cats compared with normal cats at 6 mins. Hematocrit was significantly higher in normal cats when compared with IRIS stage 3 and 4 ( P = 0.002) and uremic crisis ( P = 0.0008) cats, with no difference among groups for platelet count or MPV. The proportion of cats with positive fecal occult blood samples was significantly different between groups ( P = 0.0017); 50% uremic crisis cats, 33% IRIS stage 3 and 4 cats, and 10% IRIS stage 2 cats were positive, while no normal cats were positive. The proportion of cats with platelet clumping was significantly different between groups ( P = 0.03). Conclusions and relevance Platelet hyper-reactivity may be occurring in CKD cats experiencing a uremic crisis. The etiology of positive fecal occult blood samples in CKD cats is unclear and did not appear to be related to decreased platelet function as measured in this study and requires further investigation.

Background Focal segmental glomerulosclerosis (FSGS) is a common cause of nonimmune complex glomerulopathy and the prognosis and clinicopathologic findings associated with this condition have not been described in dogs. Objective To characterize the presentation and identify clinical factors associated with the survival of dogs with FSGS. Animals Seventy‐seven dogs diagnosed with FSGS based on evaluation of renal biopsy samples submitted to the International Veterinary Renal Pathology Service. Methods Retrospective review of medical records of dogs biopsied for evaluation of proteinuria between January 2015 and May 2017. Results The incidence of FSGS among all dogs biopsied for proteinuria was 26%. Significantly more females (48; 62.3%) than males (29; 37.7%) were affected (P = .04). At the time of biopsy, median serum creatinine concentration (SCr) was 1.2 mg/dL (range, 0.3‐8.7), median serum albumin concentration (Alb) was 2.8 g/dL (range, 1.1‐4.6), median systolic blood pressure was 153.5 mm Hg (range, 95‐260), and median urine protein : creatinine ratio was 5.9 (range, 1.4‐22). Median survival time after biopsy was 258 days (range, 26‐1003) for dogs that died from all causes (n = 32). Factors that were associated with a shorter survival time included SCr ≥ 2.1 mg/dL (P

Objectives The aim of this study was to describe the causes, clinicopathologic features and outcomes of feline protein-losing nephropathy (proteinuria secondary to glomerular disease [PLN]). Methods Kidney biopsy/necropsy samples from proteinuric cats submitted to the International Veterinary Renal Pathology Service were retrospectively reviewed. Diagnoses based on histopathology were categorized by primary disease compartment. Clinicopathologic variables at diagnosis, development of hypoalbuminemia, anemia, hypertension, azotemia and effusion/edema, and survival were compared between cats with immune-complex glomerulonephritis (ICGN) and other causes of PLN. Results Fifty-eight percent (n = 31/53) of proteinuric cats had ICGN and 74% (n = 31/42) of cats with PLN had ICGN. Cats with glomerular diseases other than ICGN had a higher median urine protein:creatinine ratio than ICGN cats (14.5 vs 6.5; P Conclusions and relevance Taken together, these data suggest that clinical suspicion for glomerular proteinuria should increase in young, male cats with higher degrees of proteinuria, and immune-mediated disease is common. Further studies are needed to determine the effect of immunosuppression on morbidity and mortality in cats with ICGN.

Background Straight- and branched-chain (BCFA) short-chain fatty acids (SCFAs) are produced by colonic microbiota and have both beneficial and deleterious effects in humans with chronic kidney disease (CKD). Fecal SCFAs in cats with CKD have not been described. Objective To characterize fecal SCFA concentrations in cats with CKD as compared to healthy geriatric cats and correlate SCFA to serum indoxyl sulfate (IS) and p-cresol sulfate (pCS) concentrations. Animals Twenty-eight cats with CKD (International Renal Interest Society [IRIS] stages 2, 3, and 4) and 11 older (≥ 8 years) healthy geriatric cats. Methods Prospective, cross-sectional study. Voided feces were analyzed using stable isotope dilution gas chromatography-mass spectrometry to determine fecal concentrations of SCFAs. Serum concentrations of IS and pCS were measured using liquid chromatography tandem mass spectrometry. Results Fecal isovaleric acid concentrations were significantly higher in CKD cats(P = .02) Cats with IRIS CKD stage 3 and 4 had significantly higher fecal isovaleric acid concentrations compared to healthy geriatric cats (P = .03), but not compared to IRIS CKD stage 2 cats. Total fecal concentrations of BCFAs were found to correlate weakly with serum creatinine concentration (rho, 0.33; P = .05), blood urea nitrogen concentration (rho, 0.40; P = .01), and pCS concentration (rho, 0.35; P = .04). Conclusions and clinical importance Fecal isovaleric acid concentrations were higher in CKD cats, particularly in late stage disease, compared to healthy geriatric cats. Fecal BCFA concentrations correlated with pCS and were higher in cats with muscle wasting, providing evidence for malassimilation of protein in CKD cats.

The ‘2021 AAFP Feline Senior Care Guidelines’ are authored by a Task Force of experts in feline clinical medicine and serve as an update and extension of those published in 2009. They emphasize the individual patient evaluation and the process of aging, with references to other feline practice guidelines for a more complete discussion of specific diseases. Focusing on each cat encourages and empowers the owner to become a part of the cat’s care every step of the way. A comprehensive discussion during the physical examination and history taking allows for tailoring the approach to both the cat and the family involved in the care. Videos and analysis of serial historical measurements are brought into the assessment of each patient. These Guidelines introduce the emerging concept of frailty, with a description and methods of its incorporation into the senior cat assessment. Minimum database diagnostics are discussed, along with recommendations for additional investigative considerations. For example, blood pressure assessment is included as a minimum diagnostic procedure in both apparently healthy and ill cats. Cats age at a much faster rate than humans, so practical timelines for testing frequency are included and suggest an increased frequency of diagnostics with advancing age. The importance of nutrition, as well as senior cat nutritional needs and deficiencies, is considered. Pain is highlighted as its own syndrome, with an emphasis on consideration in every senior cat. The Task Force discusses anesthesia, along with strategies to allow aging cats to be safely anesthetized well into their senior years. The medical concept of quality of life is addressed with the latest information available in veterinary medicine. This includes end of life considerations like palliative and hospice care, as well as recommendations on the establishment of ‘budgets of care’, which greatly influence what can be done for the individual cat. Acknowledgement is given that each cat owner will be different in this regard; and establishing what is reasonable and practical for the individual owner is important. A discussion on euthanasia offers some recommendations to help the owner make a decision that reflects the best interests of the individual cat.

Objectives Changes in bowel movements (BMs) are an important clinical sign in many diseases, including chronic kidney disease (CKD), and the purpose of this study was to collect information on BMs and fecal scores in both apparently healthy and CKD cats. A secondary aim was to assess owner awareness of BM frequency. Methods Owners were asked to complete an initial online questionnaire about their cat’s health and litter box habits (including predicted BM frequency and fecal scores) and were then asked to clean the box daily for 7 days and report results (observed frequency of BMs and fecal scores) daily. Differences in BM frequency and fecal scores between apparently normal and CKD cats were compared using the Mann–Whitney test, and predicted vs observed data were compared using the Wilcoxon signed rank test. Difference in percentage of cats defecating more or less than once daily were assessed with Fisher’s exact test. Results Survey data from 124 owners of apparently healthy cats and 43 owners of CKD cats who submitted two or more days of daily observations (in addition to the initial questionnaire) were analyzed. Eighty-five percent of apparently healthy cats were observed to defecate one or more times per day and 15% defecated less than once per day. Fifty-eight percent of CKD cats defecated one or more times per day and 42% defecated less than once per day. A significantly higher percentage of CKD cats defecated less than once per day in comparison with apparently healthy cats ( P Conclusions and relevance The observed BM frequency of cats with CKD was less than apparently healthy cats and represents a clinically important variation from normal.

Objectives The aim of this study was to evaluate the intra- and inter-rater reliability of epaxial muscle cross-sectional area measurement on feline CT images and to determine the relationship between normalized epaxial muscle area (EMA) and subjective muscle condition score (MCS). Methods Feline transverse CT images including the junction of the 13th thoracic vertebrae/13th rib head were retrospectively reviewed. Right and left epaxial muscle circumference and vertebral body height were measured and an average normalized EMA (ratio of epaxial area:vertebral height) was calculated for each image. Measurements were performed by three individuals blinded to the clinical data and were repeated 1 month later. Intra- and inter-rater reliability of EMA was assessed with concordance correlation coefficient (CCC), and Bland–Altman analysis was performed to assess bias and limits of agreement (LoA) between and within observers at different time points. In cats for which MCS data were available, EMA was compared between differing MCSs via the Kruskal–Wallis test, with Bonferroni-corrected Wilcoxon rank-sum post-hoc analysis. Results In total, 101 CT scans met the inclusion criteria for reliability analysis, 29 of which had muscle condition information available for analysis. Intra-rater EMA CCC ranged from 0.84 to 0.99 with minimal bias (range –0.16 to 0.08) and narrow LoA. Inter-rater EMA CCC ranged from 0.87 to 0.94, bias was larger (range –0.46 to 0.66) and LoA were wider when assessed between observers. Median EMA was significantly lower in cats with severe muscle atrophy (2.76, range 1.28–3.96) than in all other MCS groups ( P Conclusions and relevance Measurement of EMA on CT showed strong intra-rater reliability, and median EMA measurements were significantly lower in cats with severe muscle wasting, as assessed on physical examination. Further studies correlating EMA to lean muscle mass in cats are needed to determine whether this method may be useful to quantify muscle mass in patients undergoing a CT scan.

Objectives The aims of this study were to determine the side effect frequency and serum and urine drug concentrations of amoxicillin–clavulanic acid in cats with and without azotemic chronic kidney disease (azCKD). Methods Owners whose cats had been prescribed amoxicillin–clavulanic acid completed a survey regarding the occurrence and type of side effects, and whether treatment was altered as a result. Cats were defined as azCKD (serum creatinine concentration >2.0 mg/dl, urine specific gravity [USG] 1.035) that were receiving amoxicillin–clavulanic acid. Amoxicillin and clavulanic acid were measured with liquid chromatography coupled to tandem mass spectrometry and compared between groups with a Mann–Whitney test. Correlation between serum creatinine and drug concentrations in urine and serum was determined using Spearman’s rank test. Results Sixty-one surveys were returned (11 azCKD cats and 50 without azCKD cats). No significant difference in the presence of side effects or type of side effects was seen between groups; however, significantly more azCKD cats had more than one side effect ( P = 0.02). More owners of azCKD cats reported that an alteration in treatment plan was necessitated by side effects (55% vs 12%; P = 0.008). Urine amoxicillin was significantly lower in cats with azCKD ( P = 0.01) and serum amoxicillin trended toward significance ( P = 0.07). Serum amoxicillin concentration was positively correlated with serum creatinine ( P = 0.02; r = 0.62) and urine amoxicillin concentration was negatively correlated with serum creatinine ( P = 0.01; r = –0.65). Conclusions and relevance The data suggest that cats with azCKD have altered pharmacokinetics of amoxicillin, which may contribute to an increased incidence of multiple side effects.

Objectives The aim of this study was to assess the effect of three oral potassium supplements (potassium gluconate tablets [PGT], potassium gluconate granules [PGG] and potassium citrate granules [PCG]) on hypokalemia and serum bicarbonate in cats with chronic kidney disease (CKD). Methods Medical records (2006–2016) were retrospectively searched for cats that had been prescribed an oral potassium supplement for management of their CKD-associated hypokalemia. For inclusion, laboratory work had to be available at the time of hypokalemia diagnosis, and at recheck within 1–6 weeks. Treatment response was defined in three ways: any increase in potassium, an increase in potassium to within the normal reference interval, and an increase to >4 mEq/l. Results Thirty-seven cats met inclusion criteria (16 PGT, 11 PGG, 10 PCG). Dosing ranged from 0.21 to 1.6 mEq/kg/day for PGT, from 0.25 to 1.48 mEq/kg/day for PGG and from 0.04 to 1.34 mEq/kg/day for PCG. After supplementation, 36/37 cats had an increase in potassium, 34/37 increased to within the reference interval and 24/37 had an increase in potassium to >4 mEq/l. There was a statistically significant difference in serum potassium post-supplementation for all three treatments: PGT ( P = 0.0001), PGG ( P = 0.001) and PCG ( P = 0.002). There was a positive correlation between PGT dose and change in potassium concentration ( P = 0.04), but there was no significant correlation for PGG or PCG. In cats that had data available, serum bicarbonate increased >2 mEq/l in 1/6 PGT, 1/6 PGG and 3/4 PCG cats. Conclusions and relevance All three potassium supplements were effective in treating hypokalemia secondary to CKD in the majority of cats despite variable dosing. Data were limited to assess the alkalinizing effect and prospective studies are needed.

Renal α-enolase has variable expression in inflammatory and neoplastic diseases. Therefore, in order to define the distribution of α-enolase in renal tissues of cats, an immunohistochemistry assay was validated and described here. Tissues from 29 cats with IRIS Stage 2-4 CKD, 8 control cats2 years of age, and 4 control cats10 years of age were assessed. Interstitial nephritis was the predominant histopathological finding in the CKD group. The control cats2 years of age had moderate α-enolase immunoreactivity in tubular epithelium but staining was absent to mild in glomeruli. In contrast, α-enolase was moderate to high in tubular epithelium and glomeruli in control cats10 years of age. In cats with CKD, α-enolase was decreased in tubules that were degenerative or atrophic, similar to normal tubules in control groups, and moderate to high in glomeruli. When compared between the study groups, the results suggest that alpha-enolase decreases in damaged tubules and increases in the glomeruli of older cats prior to the development of detectable CKD. Further studies will be required to determine whether these findings relate to the pathogenesis or could be used in the diagnosis of feline CKD.

Objectives The aim of this study was to assess the appetite stimulation properties of compounded transdermal mirtazapine (CTM) in cats with chronic kidney disease (CKD). Methods Two sequential double-blind placebo-controlled crossover prospective studies were performed in client-owned cats with stable stage 2 or 3 CKD and a history of decreased appetite. In the first study nine CKD cats were randomized to receive 3.75 mg/0.1 ml CTM gel or placebo on the inner pinna every other day for 3 weeks, then, after a 4 day washout period, the cats were crossed over to the alternate 3 week treatment. In a second study, 10 CKD cats were randomized to receive 1.88 mg/0.1 ml CTM or placebo on the same schedule. Physical examination and serum biochemistry were performed before and after each treatment period, and owners kept daily logs of appetite, activity and eating behaviors. Mirtazapine concentrations in CTM gels and steady-state mirtazapine serum concentrations were measured using liquid chromatography/tandem mass spectrometry. Results Administration of both 3.75 mg and 1.88 mg CTM resulted in a statistically significant increase in weight ( P = 0.002 for both), increase in appetite ( P = 0.01 and P = 0.005, respectively), and increase in rate of food consumption ( P = 0.03 and P = 0.008, respectively). No significant difference in activity or vocalization was seen at either dose; however, individual cats experienced excessive meowing. Median weight increase for the 3.75 mg arm was 0.22 kg (range 0.04–0.44 kg), while median weight increase for the 1.88 mg arm was 0.26 kg (range –0.25 to 0.5 kg). Improvement in body condition score was seen in 5/9 cats in the 3.75 mg arm (P = 0.04) and 6/10 cats in the 1.88 mg arm (P = 0.004). Conclusions and relevance CTM increased appetite and resulted in weight gain in CKD cats despite significant inconsistencies in compounding, and may benefit cats in countries where an approved product is not available.

Background Intestinal dysbiosis has been documented in humans with chronic kidney disease (CKD) and is thought to contribute to production of the uremic toxins indoxyl sulfate (IS) and p-cresol sulfate (pCS). Characteristics of the fecal microbiome in cats with CKD and correlation to serum concentrations of uremic toxins are unknown. Objectives To characterize the fecal microbiome and measure serum IS and pCS concentrations of cats with CKD in comparison to healthy older cats. Animals Thirty client-owned cats with CKD (International Renal Interest Society stages 2-4) and 11 older (≥8 years) healthy control cats. Methods Prospective, cross-sectional study. Fecal samples were analyzed by sequencing of 16S rRNA genes and Escherichia coli quantitative PCR (qPCR). Serum concentrations of IS and pCS measured using liquid chromatography tandem mass spectrometry. Results Cats with CKD had significantly decreased fecal bacterial diversity and richness. Escherichia coli qPCR showed no significant difference in bacteria count between control and CKD cats. Cats with stage 2 (P = .01) and stages 3 and 4 (P = .0006) CKD had significantly higher serum IS concentrations compared to control cats. No significant difference found between stage 2 and stages 3 and 4 CKD. The pCS concentrations were not significantly different between CKD cats and control cats. Conclusions and clinical importance Decreased fecal microbiome diversity and richness is associated with CKD in cats. Indoxyl sulfate concentration is significantly increased with CKD, and cats with stage 2 CKD may suffer from a similar uremic toxin burden as do cats with later stage disease.

Mirtazapine is classified as a weight gain drug in cats, and the purpose of this study was to evaluate its efficacy in cats experiencing unintended weight loss. This was a multi‐center, double‐blind, placebo‐controlled, randomized clinical study in client‐owned cats ≥1 year of age, weighing ≥2 kg, with a documented loss (≥5%) in body weight. Cats were treated once daily with either 2 mg/cat mirtazapine transdermal ointment (n = 83) or placebo (n = 94) (Per Protocol population) applied to the inner surface of the pinna for 14 ± 3 days. Physical examination, body weight, complete blood count, serum chemistry, and urinalysis were performed prior to treatment and on Day 14. Changes in body weight between the mirtazapine and placebo groups were evaluated from Day 1 to Day 14 and compared using a two‐sample t test. The mean percent change in body weight was +3.9% (standard deviation ±5.4%) in the mirtazapine group and +0.4% (±3.3%) in the placebo group (p

Background Liver disease (LD) prolongs mirtazapine half‐life in humans, but it is unknown if this occurs in cats with LD and healthy cats. Hypothesis/Objectives To determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats. Animals Eleven LD and 11 age‐matched control cats. Methods Case‐control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half‐life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD. Results There was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1‐4] hours versus 1 [1‐4] hours; P = .03). The calculated half‐life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9‐61.4] hours versus 7.4 [6.7‐9.1] hours; P

Poor appetite is a common clinical complaint in patients with chronic kidney disease. Nurses can play an important role by helping to perform regular nutritional assessment to identify patients that require intervention. This article aims to discuss the importance of this clinical problem and the different mechanisms by which appetite may become abnormal in chronic kidney disease. Recent research on pharmacologic options for appetite stimulation offer new options such as mirtazapine for cats and capromorelin for dogs.

Practical relevance:Stem cell therapy is an innovative field of scientific investigation with tremendous potential for clinical application in veterinary medicine. Based on the known desirable immunomodulatory properties of mesenchymal stem cells, this therapy holds promise for the treatment of a variety of inflammatory diseases in cats.Aims:This review details our current understanding of feline stem cell biology and proposed mechanism of action. Studies performed in feline clinical trials for diseases including gingivostomatitis, chronic enteropathy, asthma and kidney disease are summarized, with the goal of providing an overview of the current status of this treatment modality and its potential for the future.

Background Monitoring urine protein:creatinine ratios (UPC) in dogs with protein-losing nephropathy (PLN) is challenging because of day-to-day variation in UPC results. Hypothesis/Objectives Determine whether single, averaged, or pooled samples from PLN dogs receiving medical treatment yield comparable UPCs, regardless of degree of proteinuria. Animals Twenty-five client-owned PLN dogs receiving medical treatment. Methods UPC ratios were prospectively measured in each dog utilizing 3 methods: single in-hospital sample (day 3), average sample (days 1–3), and pooled sample (equal pooling of urine from days 1–3). Bland-Altman analysis was performed to evaluate agreement between methods for all dogs, as well as in subgroups of dogs (UPC ≤4 or UPC >4). Results For all dogs, Bland-Altman log-transformed 95% limits of agreement were −0.07–0.18 (single versus pooled UPC), −0.06–0.16 (single versus average UPC), and −0.06–0.04 (pooled versus average UPC). For dogs with UPC ≤4, Bland-Altman 95% limits of agreement were −0.42–0.82 (single versus pooled UPC), −0.38–0.76 (single versus average UPC), and −0.27–0.25 (pooled versus average UPC). For dogs with UPC >4, Bland-Altman 95% limits of agreement were −0.17–2.4 (single versus pooled UPC), −0.40–2.2 (single versus average UPC), and −0.85–0.43 (pooled versus average UPC). Conclusions and Clinical Importance UPC ratios from all methods were comparable in PLN dogs receiving medical treatment. In PLN dogs with UPC >4, more variability between methods exists likely because of higher in-hospital results, but whether this finding is clinically relevant is unknown.

Objectives The purpose of this study was to survey owners regarding their practices and experiences with the administration of subcutaneous (SC) fluids at home to cats with chronic kidney disease (CKD) to gain insight that might help more owners be successful with the procedure. Methods A web-based survey was advertised online. Owners of 468 cats with CKD participated, 399 of whom administered SC fluids. Results Fifty-nine percent of the cats were domestic shorthairs, with >85% of the cats being 10 years of age or older. IRIS stage 3 was most commonly represented (37%). Ninety-five percent of owners said they discussed giving fluids with their veterinarian, with only 42% of those discussions involving additional educational resources. A large majority of owners (85%) said it was either an easy, somewhat easy/no stress or okay experience for them, and a large majority (89%) reported that the experience was easy/no stress, somewhat easy or okay experience for their cats. To increase tolerance, 57% said they gave a treat to their cat afterwards, and 60% said they warmed the fluids. Sixty-one percent reported using a 20 G or larger needle, with 49% saying size of needle affected tolerance. Seventy-four percent also felt that the length of time it took to administer fluids affected tolerance. One-hundred milliliters was the most commonly given fluid amount. Hydration status was monitored by 40% of owners by various methods, with 40% of those saying they skipped or added fluids based on hydration assessment. Conclusions and relevance A majority of owners gave positive feedback about their ability to learn and administer SC fluids to their cat wth CKD. Owners reported several strategies that they felt improved tolerance of fluid administration. Overall, the protocol should be tailored to the preference of the cat for best possible long-term success.

Objectives The objectives were to evaluate the pharmacokinetics (PK) of subcutaneous (SC) and intravenous (IV) dolasetron and the pharmacodynamics (PD) of SC dolasetron in healthy cats. Methods Five cats with unremarkable complete blood count, serum biochemistry and urinalyses were utilized. In the PK study, cats received 0.8 mg/kg SC and IV dolasetron in a crossover format. Serum samples were obtained via a jugular catheter at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36 and 48 h after the administration of dolasetron. Dolasetron and the active metabolite hydrodolasetron were measured using liquid chromatography/tandem mass spectrometry. Non-compartmental PK analysis was performed. In the PD study, SC dolasetron (0.8 mg/kg and 1.0 mg/kg) and saline were administered 30 mins prior to administration of 0.44 mg/kg intramuscular xylazine in a randomized three-way crossover. Number of emetic events, lip licks, time to onset of emesis and visual nausea score were scored by a blinded observer. Results In the PK study, dolasetron was quickly metabolized to the active metabolite hydrodolasetron, limiting assessment of dolasetron PK parameters. Median (range) PK parameters for IV hydrodolasetron were as follows: maximum serum concentration (Cmax) 116 ng/ml (69–316 ng/ml), time to maximum concentration (Tmax) 0.5 h (0.3–0.5 h), half-life 3.3 h (2.9–7.2 h) and area under the curve until the last measurable concentration (AUClast) 323 h/ng/ml (138–454 h/ng/ml). Median (range) PK parameters for SC hydrodolasetron were as follows: Cmax 67.9 ng/ml (60.4–117 ng/ml), Tmax 0.5 h (0.5–1.0 h), half-life 3.8 h (2.9–5.3 h) and AUClast 437 h/ng/ml (221.5–621.8 h/ng/ml). There was no significant difference in exposure to hydrodolasetron between the routes of administration. With regard to PD, when dolasetron was administered prior to xylazine, there was no significant difference in the mean number of emetic events, lip licks, time to onset of emesis or visual nausea score when compared with saline. Conclusions and relevance Administration of 0.8 mg/kg dolasetron does not maintain serum concentrations of active metabolite for 24 h. Administration of dolasetron at 0.8 mg/kg and 1 mg/kg did not prevent xylazine-induced vomiting. Additional feline dose studies are needed to determine if a higher dose is efficacious.

Background F2-isoprostanes, a biomarker of oxidant injury, increase with advancing chronic kidney disease (CKD) in humans. In cats, the relationship between CKD and oxidative stress is poorly understood. Objectives To determine whether cats with advancing CKD have increasing urinary F2-isoprostanes. Animals Control cats without evidence of CKD (≥6 years old; n = 11), and cats with IRIS stage 1 (n = 8), 2 (n = 38), 3 (n = 21), and 4 (n = 10) CKD. Methods This was a prospective observational study. Urinary F2-isoprostanes (specifically free 15-F2t-isoprostanes) normalized to urine creatinine (IsoPs) were compared among groups and tested for correlations with blood pressure, proteinuria, serum creatinine concentration, and urine specific gravity. The IsoPs also were compared between cats with and without hypertension or proteinuria, and in cats fed predominantly standard versus renal diets. Results Urinary IsoPs were increased, but not significantly, in cats with stage 1 CKD (median 263 pg/mg creatinine; range, 211–380) compared to controls (182 pg/mg; range, 80–348) and decreased significantly from stage 1 through advancing CKD (stage 2, 144 pg/mg; range, 49–608; stage 3, 102 pg/mg; range, 25–158; stage 4, 67 pg/mg; range, 26–117; P < .01). Urinary IsoPs were inversely correlated with serum creatinine (r = −0.66, P < .0001). Conclusion and Clinical Importance Urinary IsoPs are significantly higher in early CKD (stage 1) compared to cats with more advanced CKD. Additional studies are warranted to characterize oxidative stress in cats with stage 1 CKD and determine whether early antioxidant treatments have a protective effect on CKD progression.

Objectives The objective of this study was to assess the absorption of transdermal ondansetron in healthy cats. Methods Five research cats with unremarkable complete blood count, biochemistry and urinalysis were used for both single- and multiple-dose application studies. For single-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied once to the internal ear pinna. Blood samples were collected via jugular catheter over a 48 h period following administration (0, 15 mins, 30 mins, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h). For multiple-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied for five consecutive days before blood samples were obtained in the same manner. Serum was separated and frozen prior to analysis. Ondansetron was measured via liquid chromatography coupled to tandem mass spectrometry. Results Analysis revealed no clinically relevant drug levels in serum after either single- or multiple-dose administration of 4 mg transdermal ondansetron. Conclusions and relevance Transdermal application of 4 mg ondansetron does not result in clinically relevant serum concentrations of drug. Despite characteristics of the drug that imply suitability for transdermal application, this does not appear to be an acceptable method of drug delivery for this medication at this dose. This study highlights the importance of assessing the suitability of each medication for transdermal administration.

Objectives The objective of this study was to compare the ability of adipose-derived mesenchymal stem cells (aMSCs) generated from young vs geriatric cats to proliferate in culture, suppress lymphocyte proliferation and undergo senescence. Methods Adipose tissues from five young (10 years) cats were harvested and cryopreserved for subsequent aMSC isolation and culture. aMSC proliferation in culture was compared via determination of time until passage two and by 3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The immunomodulatory capacity of aMSCs was assessed using lymphocyte proliferation assays, and senescence was evaluated using senescence-associated B-galactosidase (SABG) expression. All assays were performed on aMSCs between passage two and passage three. Results aMSCs from geriatric cats took significantly longer ( P = 0.008) to reach passage two (median 11 days, range 9–22 days) compared with aMSCs from young healthy cats (median 7 days, range 6–8 days). No significant difference was detected between young and geriatric cats in terms of their ability to suppress lymphocyte proliferation. SABG expression was not significantly different between young and geriatric aMSCs. Conclusions and relevance Compared with young feline aMSCs, geriatric aMSCs are significantly impaired in their ability to rapidly proliferate to passage two following initial culture, presenting a concern for autologous therapy. Nonetheless, once the cells are expanded, young and geriatric cat aMSCs appear to be equivalent in terms of their ability to functionally suppress T-cell activation and proliferation.

Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease.

Hyperthyroidism in cats can mask changes in renal function, including chronic kidney disease (CKD), because of hyperfiltration and muscle loss. Symmetric dimethylarginine (SDMA) has been shown to increase earlier than creatinine in cats with renal dysfunction, and, unlike creatinine, SDMA is not impacted by lean muscle mass. The aim of this study was to describe the relationship between SDMA, creatinine, body weight and TT4 over time during treatment of hyperthyroidism. Cats were retrospectively identified from the US IDEXX Reference Laboratories database where TT4, SDMA and creatinine were measured on the same cat at multiple time points. A hyperthyroid treated group was identified (TT4 ≤ 4.7 μg/dL and decreased by a minimum of 2.5 μg/dL) that had body weight and laboratory results available from more than one visit, and was used to evaluate body weight, creatinine, SDMA and TT4 pre-treatment and at 1-30, 31-60, 61-90, 91-120 days post-treatment. Creatinine significantly decreased with increasing concentrations of TT4 (Spearman's ρ = -0.37, P < 0.001), whereas SDMA did not. Body weight, SDMA and creatinine concentrations significantly increased during the immediate 1-30 day post-treatment period (P < 0.012, P < 0.001, P < 0.001, respectively). During treatment creatinine continued to increase as cats gained weight. In contrast, SDMA remained stable during treatment and was comparable to age-matched control cats. Therefore, SDMA may be a more reliable biomarker of renal function than creatinine in hyperthyroid cats before and during treatment.

Stem cell therapy has tremendous potential for clinical application in the treatment of a variety of diseases in veterinary medicine. Based on the known desirable immunomodulatory properties of mesenchymal stem cells, this therapy has potential for treatment of a variety of renal diseases. This review details our current understanding of stem cell biology and proposed mechanism of action as applicable to renal disease. Studies performed in chronic kidney disease clinical trials and models of acute kidney injury are summarized with the goal of providing an overview of the current status of this treatment modality and its potential for the future.

Measurement of glomerular filtration rate (GFR) via gamma camera uptake of 99mTc-diethylenetriaminepentaacetic acid is a standard method for quantifying renal function. Aims of this retrospective, observer agreement study were to determine intra- and interobserver variation in GFR values for cats with chronic kidney disease and to determine whether renal insufficiency classification changed between observers. Guideline cut-points were established for the difference in repeated GFRs to differentiate changes caused by therapeutic effect vs. inherent variation. Included cats had a diagnosis of chronic kidney disease and had undergone GFR examinations between the years of 2010 and 2013. Twenty-nine GFR studies were sampled. Each study was read twice, 6 months apart, by two veterinary radiologists and one radiology resident. Modified Bland-Altman plots were used to investigate differences between readings 1 and 2 by observer and between pairs of observers by reading. Reliability of clinical classification was assessed through comparisons between readings and observers. Measurements were not systematically different between readings for the experienced observers but were higher in reading 1 than reading 2 for the inexperienced observer. Measurements were not systematically different between the experienced observers in reading 1 or between any two observers in reading 2. Reliability for GFR measurements was high among experienced observers; variations in GFR measurements rarely led to differences in clinical classification. Results suggested that, for experienced observers, changes in GFR values following treatment in cats with chronic kidney disease between -0.4 and 0.4 mL/min/kg may be due to inherent variability rather than treatment effect.

Objectives The objective was to describe ultrasonographic characteristics of cats with stable chronic kidney disease (CKD) and determine if these were significantly different from cats with pyelonephritis (Pyelo) and ureteral obstruction (UO), to aid in clinical assessment during uremic crisis. Methods Sixty-six cats with stable CKD were prospectively enrolled, as well as normal control cats (n = 10), cats with a clinical diagnosis of Pyelo (n = 13) and cats with UO confirmed by surgical resolution (n = 11). Renal ultrasound was performed and routine still images and cine loops were obtained. Analysis included degree of pelvic dilation, and presence and degree of ureteral dilation. Measurements were compared between groups using non-parametric one-way ANOVA with Dunn’s post-hoc analysis. Results In total, 66.6% of CKD cats had measurable renal pelvic dilation compared with 30.0% of normal cats, 84.6% of Pyelo cats and 100% of UO cats. There was no statistically significant difference in renal pelvic widths between CKD cats and normal cats, or CKD cats and Pyelo cats. On almost all measurement categories, UO cats had significantly greater renal pelvic widths compared with CKD cats and normal cats ( P Conclusions and relevance No significant difference in renal pelvic widths between CKD cats and Pyelo cats was seen. These data suggest CKD cats should have a baseline ultrasonography performed so that abnormalities documented during a uremic crisis can be better interpreted.

A 7 yr old, male, castrated, Yorkshire terrier was presented on emergency for an acute onset of seizure activity. The owner also reported that the dog had previously exhibited other symptoms, including intermittent vomiting, diarrhea, and anorexia for several yr. The initial workup revealed a marked decrease in ionized calcium and total protein. Further diagnostics revealed decreases in magnesium, 25 hydroxyvitamin D, albumin, and globulins, and an increased parathyroid hormone level. Intestinal biopsies revealed inflammatory bowel disease and lymphangiectasia. The dog received intravenous calcium gluconate for treatment of hypocalcemia followed by oral calcium and vitamin D supplementation. Seizure activity ceased once calcium levels approached the normal range. Medical and dietary therapy for lymphangiectasia and inflammatory bowel disease consisted of prednisone, rutin, and a low-fat diet. Decreased serum total ionized calcium levels have been reported previously in dogs with protein-losing enteropathies. Typically, the hypocalcemia is not associated with clinical signs. Severe clinical signs of hypocalcemia are rarely reported in dogs with protein-losing enteropathy, but seizures, facial twitching, and tremors can occur. When presented with a dog with a history of seizure activity, panhypoproteinemia, and hypocalcemia, protein-losing enteropathy should be included on the list of differential diagnoses.

Single and multiple dose pharmacokinetics (PK) of mirtazapine transdermal ointment applied to the inner ear pinna of cats were assessed. Study 1 was a randomized, cross-over single dose study (n = 8). Cats were treated once with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner ear pinna (treatment) or administered orally (control) and then crossed over after washout. Plasma was collected predose and at specified intervals over 96 hr following dosing. Study 2 was a multiple dose study (n = 8). Cats were treated daily for 14 days with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner pinna. Plasma was collected on Day 13 predose and at specified intervals over 96 hr following the final dose. In Study 1, single transdermal administration of mirtazapine resulted in mean Tmax = 15.9 hr, Cmax = 21.5 ng/mL, AUC0-24 = 100 ng*hr/mL, AUC0-∞ = 260 ng*hr/mL and calculated half-life = 26.8 hr. Single oral administration of mirtazapine resulted in mean Tmax = 1.1 hr, Cmax = 83.1 ng/mL, AUC0-24 = 377 ng*hr/mL, AUC0-∞ = 434 ng*hr/mL and calculated half-life = 10.1 hr. Mean relative bioavailability (F) of transdermal to oral dosing was 64.9%. In Study 2, daily application of mirtazapine for 14 days resulted in mean Tmax = 2.1 hr, Cmax = 39.6 ng/mL, AUC0-24 = 400 ng*hr/mL, AUC0-∞ = 647 ng*hr/mL and calculated half-life = 20.7 hr. Single and repeat topical doses of a novel mirtazapine transdermal ointment achieve measurable plasma concentrations in cats.

A 7-month-old female domestic shorthair cat was diagnosed with chronic regenerative hemolytic anemia characterized by increased osmotic fragility of unknown etiology. At 13 months of age, the cat was evaluated for acute collapse. The cat was icteric with severe hyperbilirubinemia but no hematocrit changes. Severe obtundation and lateral recumbency progressed to tetraparesis and loss of proprioception in all 4 limbs, and a cerebellar or brainstem lesion was suspected. Postmortem examination revealed suppurative cholangiohepatitis and acute neuronal necrosis in the nuclei of the brainstem and cerebellum, consistent with bilirubin encephalopathy. This is the first known occurrence of cholangiohepatitis and bilirubin encephalopathy in an adult cat with chronic hemolytic anemia. Although rare, bilirubin encephalopathy should be considered a possible sequela to hyperbilirubinemia in adult patients. It remains unknown whether increased osmotic fragility was related to the cholangiohepatopathy.

Objective—To evaluate differences in pulse rate, rectal temperature, respiratory rate, and systolic arterial blood pressure in dogs between the home and veterinary hospital environments. Design—Prospective observational study. Animals—30 client-owned healthy dogs. Procedures—Study dogs had respiratory rate, pulse rate, rectal temperature, and systolic arterial blood pressure measured in their home environment. Dogs were then transported to the veterinary hospital, and measurements were repeated. Results—Significant differences in blood pressure, rectal temperature, and pulse rate were observed between measurements obtained in the home and hospital environments. Mean blood pressure increased by 16% (95% confidence interval [CI], 8.8% to 24%), rectal temperature increased by < 1% (95% CI, 0.1% to 0.6%), and pulse rate increased by 11% (95% CI, 5.3% to 17.6%). The number of dogs panting in the hospital environment (19/30 [63%]) was significantly higher than the number of dogs panting in the home environment (5/30 [17%]) Conclusions and Clinical Relevance—Results of the present study suggested that practitioners should consider stress from transportation and environmental change when canine patients have abnormalities of vital signs on initial examination, and the variables in question should be rechecked before a definitive diagnosis of medical illness is reached or extensive further workup is pursued.

Objectives The objective of this study was to measure drug exposure and clinical effects after administration of transdermal mirtazapine (TMZ) in healthy cats. Methods Phase I: seven healthy research cats received (1) 3.75 mg and 7.5 mg TMZ once aurally with 48 h serum sampling (serum samples were obtained via the jugular catheter at 0, 0.5, 1, 2, 5, 9, 12, 24, 36 and 48 h); (2) 7.5 mg TMZ and placebo daily aurally for 6 days then 48 h serum sampling; (3) 1.88 mg mirtazapine orally once with serum sampling at 1, 4 and 8 h. Phase II: 20 client-owned cats were enrolled in a randomized, double-blind, placebo-controlled, three-way crossover clinical effect study. Treatments consisted of 6 days of aural 7.5 mg TMZ or placebo gel at home, and 1.88 mg mirtazapine orally once in the clinic. Owners documented appetite, rate of food ingestion, begging activity and vocalization daily at home. On day 6, food consumed, activity and vocalization were documented in hospital, and trough and peak serum mirtazapine levels were obtained. Serum mirtazapine and gel concentrations were measured using liquid chromatography/tandem mass spectrometry. Results Phase I: administration of TMZ achieved measureable serum mirtazapine concentrations. Area under the curve0–48 of multidose 7.5 mg TMZ was significantly higher than single-dose 1.88 mg oral mirtazapine (OMZ) ( P = 0.02). Phase II: client-owned cats administered TMZ had a significant increase in appetite ( P = 0.003), rate of food ingestion ( P = 0.002), activity ( P = 0.002), begging ( P = 0.002) and vocalization ( P = 0.002) at home. In hospital there was a significant increase in food ingested with both TMZ and OMZ compared with placebo ( P Conclusions and relevance TMZ 7.5 mg daily achieves measureable serum concentrations and produces significant appetite stimulation despite variance in compounded gel concentrations, but side effects denote a lower dose is indicated.

Objectives Maropitant is commonly used for acute vomiting. A pharmacokinetic and toxicity study in cats indicated that longer term usage appears safe. The aim of this study was to assess the efficacy of maropitant for management of chronic vomiting and inappetence associated with feline chronic kidney disease (CKD). Methods Forty-one cats with stable International Renal Interest Society Stage II or III CKD, no known concurrent illness, and a complaint of chronic vomiting and inappetence attributed to CKD were enrolled in a randomized, placebo-controlled, blinded clinical study. A complete blood count, serum biochemistry, urinalysis, urine culture, T4 and blood pressure were required for entry. Maropitant was administered at a dose of 4 mg orally (median 1.1 mg/kg, range 0.6–2.9 mg/kg) daily for 2 weeks. Owners kept daily logs of vomiting incidence, appetite and activity scores. Physical examination, weight, body condition score and serum biochemistry were performed before and after the trial period. Mann–Whitney statistics were used to compare treatment groups. Results Thirty-three cats successfully completed the trial: 21 cats received the drug (nine Stage II cats, 12 Stage III cats) and 12 cats received placebo (seven Stage II cats, five Stage III cats). There was a statistically significant decrease in vomiting in cats with CKD that received maropitant ( P Conclusions and relevance Maropitant was demonstrated to palliate vomiting associated with CKD, and may be helpful in the nutritional management of cats with CKD.