Evaluation of a urine dipstick protein to urine specific gravity ratio for the detection of proteinuria in dogs and cats.

BACKGROUND: The utility of urine dipsticks for the quantification of proteinuria is limited because of the influence of urine specific gravity (USG). To circumvent the need for urine protein creatinine ratios (UPCR) some have proposed a calculated dipstick urine protein to USG ratio (DUR) for the detection of proteinuria. However, the performance of DUR has not been evaluated in veterinary patients. OBJECTIVES: Evaluate the correlation between DUR and UPCR, while also assessing the effect of urine characteristics on this relationship and evaluating the performance of DUR in detecting proteinuria. ANIMALS: Urine samples from 308 dogs and 70 cats. METHODS: Retrospective cohort study of urinalyses and UPCRs from dogs and cats collected between 2016 and 2021. RESULTS: Both canine and feline urine samples showed a positive moderate correlation between the UPCR and DUR. The correlation was not influenced by the presence of active urine sediment, glucosuria, or urine pH. In detecting canine urine samples with a UPCR >0.5, an optimal DUR of 1.4 had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89%, 83%, 96%, and 63%, respectively. In detecting feline urine samples with a UPCR >0.4, an optimal DUR of 2.1 had sensitivity, specificity, PPV, and NPV of 70%, 100%, 100%, and 75%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of the DUR can be a relatively reliable method for identification of proteinuria. However, given its poor NPV, the DUR cannot be recommended for exclusion of proteinuric patients.

Retrospective evaluation of the etiology and clinical characteristics of peripheral edema in dogs.

BACKGROUND: The prevalence and clinical characteristics of different etiologies of peripheral edema in dogs are unknown. HYPOTHESIS/OBJECTIVES: To determine the prevalence of different etiologies of peripheral edema, describe clinical characteristics that vary among etiologies, and report survival times. ANIMALS: Five hundred twenty-seven dogs with peripheral edema. METHODS: Retrospective medical record review. Differences in clinical variables among etiology groups were assessed by Kruskal-Wallis testing with post hoc pairwise Dunn's testing and Chi-square testing with Monte Carlo simulation. RESULTS: The most common etiologies of peripheral edema in dogs were vasculitis (n = 193, 37%), lymphatic/venous obstruction (LVO; 114, 22%), and hypoalbuminemia (94, 18%). Right-sided congestive heart failure (R-CHF) was uncommon (25, 5%). Edema was localized in 377 (72%) dogs and generalized in 142 (27%) dogs, and hypoalbuminemia was more likely to cause generalized edema compared to LVO or vasculitis (P < .0001). Concurrent abdominal effusion (155, 29%) was more common than pleural (77, 15%) or pericardial (12, 2%) effusion. Abdominal and pleural effusion occurred more commonly in dogs with hypoalbuminemia or R-CHF compared to LVO or vasculitis (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Distribution of edema, concurrent cavitary effusions, and clinicopathological data can help predict the underlying etiology of peripheral edema in dogs.

Changes in symmetric dimethylarginine and glomerular filtration rates in hyperthyroid cats undergoing radioiodine therapy.

OBJECTIVES: The aims of this study were to evaluate concentrations of symmetric dimethylarginine (SDMA) in hyperthyroid cats before and after radioiodine treatment, and to compare results with other variables used to assess kidney function in cats (creatinine, urine specific gravity [USG] and glomerular filtration rate [GFR] measured by renal scintigraphy). METHODS: Thirteen cats diagnosed with hyperthyroidism based on clinical signs and increased serum total thyroxine (TT4) were included in this prospective study. Study design included physical examination, complete blood count, serum chemistry, TT4, urinalysis and SDMA before treatment (T0) and at 1 month (T1) and 3 months post-treatment (T3). GFR was quantified by renal scintigraphy at T0 and T3. RESULTS: Median GFR decreased significantly from baseline (3.18 ml/kg/min; range 1.35-4.87) at T3 (2.22 ml/kg/min; range 1.81-3.42 [P = 0.005]). While median creatinine and serum urea nitrogen increased post-treatment (creatinine: T0 = 0.8 mg/dl [range 0.4-1.1], T1 = 1.3 mg/dl [range 0.9-2]; T3 = 1.65 mg/dl [range 0.8-2.8]; P <0.001; serum urea nitrogen: T0 = 23 mg/dl [range 15-26]; T1 = 27 mg/dl [range 20-40]; T3 = 27.5 mg/dl [range 20-36]; P <0.001), SDMA and USG did not change significantly (SDMA: T0 = 11 µg/dl [range 7-15]; T1 = 12 µg/dl [range 6-16]; T3 = 10.5 µg/dl [range 8-21]; P = 0.789; USG: T0 = 1.030 [range 1.011-1.059]; T1 = 1.035 [range 1.012-1.044]; T3 = 1.030 [range 1.007-1.055]; P = 0.792). CONCLUSIONS AND RELEVANCE: Our data suggest that factors other than GFR may affect serum SDMA in hyperthyroid cats and that SDMA does not offer an advantage over other biomarkers traditionally used to predict changes in renal function following radioiodine therapy.

Prevalence of aldosterone breakthrough in dogs receiving renin-angiotensin system inhibitors for proteinuric chronic kidney disease.

BACKGROUND: The influence of aldosterone breakthrough (ABT) on proteinuria reduction during renin-angiotensin system (RAS) inhibition for spontaneous proteinuric chronic kidney disease (CKDP ) has not been determined in dogs. OBJECTIVES: Determine whether ABT occurs in dogs with CKDP and if it is associated with decreased efficacy in proteinuria reduction during RAS inhibitor treatment. ANIMALS: Fifty-six client-owned dogs with CKDP and 31 healthy client-owned dogs. METHODS: Prospective, multicenter, open-label clinical trial. Dogs were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker alone or in combination at the attending clinician's discretion and evaluated at 5 time points over 6 months. Healthy dogs were used to determine the urine aldosterone-to-creatinine ratio cutoff that defined ABT. The relationship of ABT (present at ≥50% of visits) and proteinuria outcome (≥50% reduction in urine protein-to-creatinine ratio from baseline at ≥50% of subsequent visits) was evaluated. Mixed effects logistic regression was used to evaluate the relationship between clinical variables and outcomes (either successful proteinuria reduction or ABT). RESULTS: Thirty-six percent (20/56) of dogs had successful proteinuria reduction. Between 34% and 59% of dogs had ABT, depending on the definition used. Aldosterone breakthrough was not associated with proteinuria outcome. Longer duration in the study was associated with greater likelihood of successful proteinuria reduction (P = .002; odds ratio, 1.6; 95% confidence interval [CI], 1.2-2.2). CONCLUSIONS AND CLINICAL IMPORTANCE: Aldosterone breakthrough was common in dogs receiving RAS inhibitors for CKDp but was not associated with proteinuria outcome.

Case Report: Successful Management and Long-Term Follow-Up of Bilateral Ureteral Ligation in a Dog Secondary to Cryptorchid Castration Utilizing Bilateral Ureteral Stents and a Neoureterocystostomy Procedure.

Objective: To report the successful management of the bilateral ureteral obstruction secondary to ureteral ligation during unilateral cryptorchid surgery in a dog with the utilization of bilateral ureteral stent placement and a neoureterocystostomy procedure. Summary: A 7-month-old male-castrated Weimaraner weighing 30 kg was presented to a university teaching hospital for evaluation of a 4-day history of lethargy, vomiting, and stranguria following exploratory laparotomy for a left-sided unilateral cryptorchid castration. Based on the concurrent presence of severe azotemia and ultrasonographic findings of bilateral hydronephrosis and hydroureter, the dog was diagnosed with the suspected bilateral ureteral obstruction. The dog underwent a laparotomy which revealed bilateral ureteral ligation which was corrected with a left-sided neoureterocystostomy and right-sided retrograde ureteral stent placement. Subsequent placement of a left-sided ureteral stent due to complications with the neoureterocystostomy site was performed later. Ultimately, both ureteral stents were able to be removed a few months later. The dog was clinically doing well with a baseline creatinine of 1.5 mg/dl (132.6 µmol/L) 532 days following initial bilateral ureteral ligation. New or Unique Information Provided: This case report describes the successful long-term management of iatrogenic bilateral ureteral obstructions in a male dog using a combination of bilateral ureteral stents and neoureterocystostomy.

Characterization of recessed vulvas in dogs.

OBJECTIVE: To determine the prevalence of vulvar recession in a large population of dogs and to compare the reproductive and physical differences between dogs with and without recessed vulvas. ANIMALS: 250 female dogs presenting to a tertiary referral institution. PROCEDURES: Female dogs > 6 months of age presenting to a tertiary referral institution were enrolled. At enrollment, a full medical history was obtained with particular emphasis on the presence of lower urinary tract (LUT) disease in the 3 months prior to presentation. All dogs underwent a full physical examination including perivulvar cytologic examination and scoring of the degree of perivulvar skin coverage on the basis of an 8-point scale. Dogs with scores of ≥ 7 were classified as having recessed vulvas. When available, urinalysis data were also included. RESULTS: Recessed vulvas were identified in 36 of 250 (14%) dogs. Dogs with recessed vulvas had significantly higher body condition scores and body weights than unaffected dogs. In addition, recessed vulvas were more common in spayed than sexually intact dogs. Dogs spayed at ≤ 1 year of age were almost 3 times as likely to have vulvar recession, compared with dogs spayed at > 1 year of age. No significant difference was identified between affected and unaffected dogs with respect to the prevalence of LUT signs, urinary tract infections, or perivulvar dermatitis. CONCLUSIONS AND CLINICAL RELEVANCE: Although recessed vulvas were relatively common in dogs, they did not appear to be associated with an increased risk of LUT disease or perivulvar dermatitis.

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease.

This multi-institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client-owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8-58.2) kg and in 31 cats was 3.9 (2.4-6.1) kg included in pharmacokinetic analyses. The dose, average steady-state serum concentrations (CSS ), and oral clearance in dogs were 14.2 (4.5-21.3) mg/kg/d, 26.8 (3.8-61.5) µg/mL, and 0.63 ml min-1  kg-1 , respectively, and in cats were 18.6 (8.2-40.0) mg/kg/d, 32.1 (1.9-103.5) µg/mL, and 0.61 ml min-1  kg-1 , respectively. Random inter-animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median CSS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50-100 mg total daily dose in cats are recommended to achieve median CSS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on CSS (therapeutic drug monitoring) and treatment failure should be considered.

Hypocholesterolemia in cats: a multicenter retrospective study of 106 cats.

OBJECTIVES: The aim of this study was to describe the clinicopathologic findings and associated diseases found in a population of hypocholesterolemic cats referred to two tertiary care facilities. METHODS: An electronic medical record search was performed at two veterinary university referral centers to identify cats with serum cholesterol values below the reference interval between January 2004 and 2016. Clinicopathologic data were reviewed for each case and cats were classified into specific disease categories based on clinical diagnosis. Median cholesterol values were compared between disease categories, as well as between survivors and non-survivors. RESULTS: In total, 106 hypocholesterolemic cats were included. The median age of the cats was 6 years (range 0.24-18 years). The most common disease categories were gastrointestinal (25.9%), hepatobiliary (19.8%), hematologic (14.8%) and urogenital (14.8%). Though median serum cholesterol values did not differ significantly between survivors and non-survivors, cats with concurrent hypoalbuminemia were at higher risk (odds ratio 15.6, 95% confidence interval 5.2-46.6; P <0.0001) of not surviving to discharge than cats with normal serum albumin concentrations. CONCLUSIONS AND RELEVANCE: Taken together, our data suggest that while the degree of hypocholesterolemia did not appear to influence survival rates, the concurrent presence of hypocholesterolemia and hypoalbuminemia was associated with a worse prognosis.

Clinicopathologic, hemodynamic, and echocardiographic effects of short-term oral administration of anti-inflammatory doses of prednisolone to systemically normal cats.

OBJECTIVE: To evaluate the clinicopathologic, hemodynamic, and echocardiographic effects of short-term administration of anti-inflammatory dosages of prednisolone to systemically normal cats. ANIMALS: 10 cats with allergic dermatitis and 10 healthy control cats. PROCEDURES: Cats with allergic dermatitis were randomly allocated to 2 groups and received 2 dosages of prednisolone (1 and 2 mg/kg/d, PO, for 7 days) in a crossover design followed by 9-day tapering and 14-day washout periods. Each prednisolone-treated cat was matched to a healthy control cat on the basis of sex, neuter status, age (± 1 year), and body weight (± 10%). Control cats received no treatment during the 35-day observation period. Clinicopathologic, echocardiographic, and hemodynamic variables were measured at baseline (day 0) and predetermined times during and after prednisolone administration and compared within and between the 2 treatment groups. RESULTS: Prednisolone-treated cats had expected clinicopathologic alterations (mild increases in neutrophil and monocyte counts and serum concentrations of albumin, cholesterol, and triglycerides) but systolic arterial blood pressure; blood glucose, serum potassium, and cardiac biomarker concentrations; urinary sodium excretion; and echocardiographic variables did not differ significantly from baseline at any time. Statistically significant, albeit clinically irrelevant, increases in blood glucose and N-terminal pro-B-type natriuretic peptide concentrations were observed between baseline and the prednisolone pharmacokinetic steady state (7 days after initiation) only when the 2-mg/kg dosage was administered. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated short-term oral administration of anti-inflammatory dosages of prednisolone did not cause relevant hemodynamic, echocardiographic, or diabetogenic effects in systemically normal cats with allergic dermatitis.

Seroprevalence of Leptospira spp., Toxoplasma gondii, and Dirofilaria immitis in Free-Roaming Cats in Iowa.

By the nature of their environment and behavior, free-roaming cats are at increased risk of exposure to a wide range of pathogens compared with client-owned cats. Consequently, free-roaming cats can act as a reservoir for possible zoonotic infections. In this study, 140 cats were prospectively recruited over a 12-month period from a free-roaming cat spay and neuter clinic and a local animal shelter in the state of Iowa. The presence of antileptospiral antibodies was measured using a microscopic agglutination test against six leptospiral serovars (canicola, pomona, icterhemorrhagiae, bratislava, hardjo, and grippotyphosa). In addition, serum samples were tested for the presence of antibodies against Toxoplasma gondii and Dirofilaria immitis using an ELISA and lateral flow immunoassay, respectively. Serum samples from 12/139 cats (8.6%) were positive for the leptospiral serovars tested, with bratislava having the highest prevalence. Cats were more likely to be positive in the spring than in the fall or summer. Positive titers to T. gondii and D. immitis were present in 42/140 cats (30%) and 9/140 cats (6.4%), respectively. Cats >72 months of age were more likely to be seropositive to T. gondii than cats in younger age groups. Feline Leptospira spp. seroprevalence was higher in this Midwestern location than has previously been reported elsewhere in the United States. Contrary to previously reported seasonal trends, this population was more likely to be Leptospira spp. seropositive in the spring rather than fall or summer. Seroprevalence of D. immitis in this geographical location was substantially lower than previous reports of free-roaming cats in the United States.

Severe Disseminated Necrotizing and Granulomatous Lymphadenitis and Encephalitis in a Dog Due to Sporotrichum pruinosum (Teleomorph: Phanerochaete chrysosporium).

A 9-year-old female mixed breed dog presented for an acute onset of anorexia, vomiting, and cough. Initial examination and diagnostics revealed a large multilobular cranial mediastinal mass with unidentified fungal organisms on cytology. The disease progressed in spite of therapy until the dog was euthanized 8 months later. Gross necropsy findings were a large multilobular intrathoracic mass, mild pleuritis, and generalized lymphadenopathy. Histologic evaluation showed granulomatous inflammation and necrosis with numerous 20- to 70-micron, periodic acid-Schiff- and Gomori methenamine silver-positive spherules effacing lymph node parenchyma, as well as severe inflammation within the midbrain. Endosporulation was a common finding, and large numbers of fungal hyphae were also present in affected areas. Ribosomal RNA gene sequencing found 100% identity to published sequences of Phanerochaete chrysosporium, the teleomorph form of Sporotrichum pruinosum. This is the first published report of disease caused by natural infection with this basidiomycete organism in animals.

Clinical Response and Side Effects Associated with Testosterone Cypionate for Urinary Incontinence in Male Dogs.

Urethral sphincter mechanism incompetence (USMI) is reported much more seldom in male dogs than in female dogs. The few existing reports evaluating the efficacy of medical therapy in controlling USMI in males have demonstrated limited success. In this case series, we report the effect of testosterone cypionate, given at a median dose of 1.5 mg/kg intramuscularly every 4 wk, in eight male dogs with USMI. Response was evaluated through the review of medical records and telephone interviews with the clients. Based on owners' assessments, a good to excellent response was reported in three of eight dogs (38%), a slight response was reported in one of eight dogs (12%), and a poor response was reported in four of eight dogs (50%). Adverse effects were not reported, and benefit was judged sufficient to continue therapy in two cases. The results reported in this case series suggest that testosterone cypionate might be an effective and safe treatment option for male dogs with USMI.

Isolation and characterization of atypical Listeria monocytogenes associated with a canine urinary tract infection.

Listeria monocytogenes, a well-described cause of encephalitis and abortion in ruminants and of food-borne illness in humans, is rarely associated with disease in companion animals. A case of urinary tract infection associated with an atypical, weakly hemolytic L. monocytogenes strain is described in a diabetic dog. The serotype of the L. monocytogenes isolate was determined to be 1/2a (3a), with the multilocus genotyping pattern 2.72_1/2a. A nucleotide substitution (Gly145Asp) was detected at residue 145 in the promoter prfA region. This residue is within the critical helix-turn-helix motif of PrfA. The source of the L. monocytogenes strain remains unknown, and the dog recovered after a 4-week course of cephalexin (30 mg/kg orally twice daily).

Infective endocarditis in 13 cats.

INTRODUCTION: To describe the clinical presentation, clinicopathological abnormalities and outcomes of a series of cats diagnosed with infective endocarditis (IE) at two tertiary care referral institutions. ANIMALS: Thirteen client-owned cats presenting to the cardiology or emergency services of tertiary referral institutions with a diagnosis of endocarditis based on the modified Duke criteria. MATERIALS AND METHODS: Retrospective case series. Medical records were reviewed to extract relevant data. In addition, cases that had cardiac tissue available were evaluated by polymerase chain reaction for the presence of Bartonella DNA. RESULTS: Prevalence of feline IE was 0.007%. Cats with endocarditis tended to be older (median age: 9 years, range: 2-12 years) and no sex or breed was overrepresented. Commonly encountered clinical signs included respiratory distress (n = 5) and locomotor abnormalities of varying severity (n = 5). Echocardiographic examination detected valvular lesions consistent with endocarditis on the aortic (n = 8) or mitral (n = 5) valves. Nine cats were diagnosed with congestive heart failure at the time of endocarditis diagnosis. Overall, prognosis was grave with a median survival time of 31 days. CONCLUSIONS: In contrast to dogs, cats with IE typically present with clinical signs consistent with cardiac decompensation and locomotor abnormalities suggestive of either thromboembolic disease or inflammatory arthritis. Given the advanced state of disease when diagnosis typically occurs, prognosis is grave.

Increased resistance to nitrogen mustards and antifolates following in vitro selection of murine fibroblasts and primary hematopoietic cells transduced with a bicistronic retroviral vector expressing the rat glutathione S-transferase A3 and a mutant dihydrofolate reductase.

We have constructed a retroviral bicistronic vector, MFG/GID, that transduces the expression of both the A3 isoform of the rat glutathione S-transferase (GST A3), and the tyr-22 variant of the human dihydrofolate reductase (DHFR(L22Y)). Transduction of murine 3T3 fibroblasts with this vector increased their in vitro resistance to chlorambucil (1.8-fold) and trimetrexate (TMTX) (748-fold). TMTX selection of a mixed population of 20% GID-transduced NIH 3T3 cells and 80% control cells resulted in a marked increase in the GST peroxidase activity associated with the GST A3 isoform (17.7-fold). MFG/GID-transduced primary clonogenic murine hematopoietic progenitor cells were likewise more resistant to TMTX and chlorambucil than control beta-gal-transduced cells. Selecting GID-transduced hematopoietic cells with a combination of TMTX and a nucleoside transport inhibitor resulted in a marked increase in resistance upon re-exposure to TMTX (99% survival). Similarly, GID-transduced hematopoietic cells selected with TMTX were more resistant to chlorambucil, with 40% survival at a drug concentration that killed practically all control cells. These results suggest that antifolate-mediated selection of MFG/GID-transduced hematopoietic cells could be used as a mean to enrich the population of transduced cells prior to or following transplantation, thus potentially conferring in vivo chemoprotection to nitrogen mustards and antifolates.

Fas engagement induces neurite growth through ERK activation and p35 upregulation.

Fas (also known as CD95), a member of the tumour-necrosis receptor factor family of 'death receptors', can induce apoptosis or, conversely, can deliver growth stimulatory signals. Here we report that crosslinking Fas on primary sensory neurons induces neurite growth through sustained activation of the extracellular-signal regulated kinase (ERK) pathway and the consequent upregulation of p35, a mediator of neurite outgrowth. In addition, functional recovery after sciatic nerve injury is delayed in Fas-deficient lpr mice and accelerated by local administration of antibodies against Fas, which indicates that Fas engagement may contribute to nerve regeneration in vivo. Our findings define a role for Fas as an inducer of both neurite growth in vitro and accelerated recovery after nerve injury in vivo.