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.

Effects of low-dose meloxicam in cats with chronic kidney disease.

OBJECTIVES: Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival. This study aimed to prospectively evaluate the renal effects of low-dose meloxicam treatment (0.02 mg/kg/day) over 6 months in cats with chronic kidney disease (CKD). METHODS: Twenty-one cats with stable International Renal Interest Society stage 2 or 3 CKD were recruited and randomized to placebo or meloxicam groups. Cats were evaluated at baseline and at 1, 3 and 6 months, including blood pressure, chemistry, symmetric dimethylarginine (SDMA), glomerular filtration rate (GFR), urinalysis, urine protein:creatinine ratio (UPC), urine transforming growth factor-beta (ß):creatinine ratio, urine clusterin, urine cystatin B and serum inosine. RESULTS: No statistical difference was observed in systolic blood pressure, blood urea nitrogen, creatinine, SDMA, GFR, urine transforming growth factor-ß:creatinine ratio, urine clusterin, urine cystatin B or serum inosine in cats receiving meloxicam vs placebo. Mean UPC was greater in the meloxicam group (0.33) than the placebo group (0.1) at 6 months (P = 0.006). Four cats had meloxicam discontinued owing to potential (mainly gastrointestinal) adverse effects. CONCLUSIONS AND RELEVANCE: No decline in renal excretory function was observed when meloxicam was administered to cats with CKD. However, gastrointestinal adverse effects were observed, and cats that received meloxicam had greater proteinuria at 6 months than cats that received placebo. As proteinuria is associated with negative outcomes (progression of azotemia and hypertension) in cats with CKD, this finding suggests that meloxicam should be used with caution in cats with CKD and UPC monitored. Until further research is available, clinicians should weigh the risk of potential increased proteinuria against quality of life benefits when considering meloxicam for analgesia in cats with renal disease.

Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats.

Effects of feline hyperthyroidism on kidney function: a review.

Chronic kidney disease and hyperthyroidism are two commonly diagnosed conditions in the geriatric feline population, and are often seen concurrently. Management of both diseases is recommended; however, the physiologic implications of both diseases must be understood to ensure the most favorable outcome for each patient. This report reviews the complex interplay between hyperthyroidism and kidney function, as well as the effects of hyperthyroid therapy on kidney function.

The renal effects of NSAIDs in dogs.

The quality of life for dogs with osteoarthritis can often be improved with nonsteroidal anti-inflammatory drugs (NSAIDs); however, the number of adverse drug events associated with NSAID use reported to the Federal Drug Administration Center for Veterinary Medicine is higher than that for any other companion animal drug. Of those events, adverse renal reactions are the second most reported. NSAIDs produce pharmacologic effects via inhibition of cyclooxygenase (COX), which decreases production of prostanoids. Prostaglandins are synthesized by both the COX-1 and COX-2 enzymes in the healthy kidney and influence renal blood flow, glomerular filtration rate, renin release, and Na excretion. There are important species differences in the renal expression of COX-1 and COX-2. For example, dogs have higher basal levels of COX-2 expression in the kidney compared with humans. In addition, in dogs with chronic kidney disease, an increase in COX-2 expression occurs and synthesis of prostaglandins shifts to the COX-2 pathway. For those reasons, NSAIDs that target COX-2 may be expected to adversely affect renal function in dogs, especially dogs with chronic kidney disease. The purpose of this review was to evaluate the literature to report the renal effects of NSAIDs in dogs.

Diagnosis and management of feline hyperthyroidism: current perspectives.

Previous and ongoing research has provided insights to the pathophysiology and diagnosis of hyperthyroidism as well as new treatment modalities. This paper reviews the etiology, clinical presentation, and clinicopathologic changes associated with hyperthyroidism, and provides a thorough explanation of confirmatory testing and treatment options.

Acute and chronic effects of tepoxalin on kidney function in dogs with chronic kidney disease and osteoarthritis.

OBJECTIVE: To determine whether tepoxalin alters kidney function in dogs with chronic kidney disease (CKD). ANIMALS: 16 dogs with CKD (International Renal Interest Society stage 2 or 3) and osteoarthritis. PROCEDURES: Kidney function was assessed via serum biochemical analysis, urinalysis, urine protein-to-creatinine concentration ratio, urine γ-glutamyl transpeptidase-to-creatinine concentration ratio, iohexol plasma clearance, and indirect blood pressure measurement twice before treatment. Dogs received tepoxalin (10 mg/kg, PO, q 24 h) for 28 days (acute phase; n = 16) and an additional 6 months (chronic phase; 10). Recheck examinations were performed weekly (acute phase) and at 1, 3, and 6 months (chronic phase). Kidney function variables were analyzed via repeated-measures ANOVA. RESULTS: There was no difference over time for any variables in dogs completing both phases of the study. Adverse drug events (ADEs) resulting in discontinuation of tepoxalin administration included increased serum creatinine concentration (1 dog; week 1), collapse (1 dog; week 1), increased liver enzyme activities (1 dog; week 4), vomiting and diarrhea (1 dog; week 8), hematochezia (1 dog; week 24), and gastrointestinal ulceration or perforation (1 dog; week 26). Preexisting medical conditions and concomitant drug use may have contributed to ADEs. Kidney function was not affected in the latter 5 dogs. Discontinuation of tepoxalin administration stabilized kidney function in the former dog and resolved the ADEs in 4 of the 5 latter dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Tepoxalin may be used, with appropriate monitoring, in dogs with International Renal Interest Society stage 2 or 3 CKD and osteoarthritis.

UTIs in small animal patients: part 2: diagnosis, treatment, and complications.

There are multiple considerations when making a treatment plan for patients with urinary tract infections (UTIs). In part 2 of this review the authors discuss the clinical signs, diagnosis, treatment, and complications associated with bacterial UTIs in dogs and cats. Part 1 of this review summarized etiology and pathogenesis (see the Jan/Feb 2013 issue of the Journal of the American Animal Hospital Association).

Carotid artery pseudoaneurysm in a cat.

UNLABELLED: CLINICAL SUMMARY: A 4-month-old female intact domestic shorthair cat presented to Kansas State University Veterinary Medical Teaching Hospital for investigation of a large, firmly adhered mass in the left mid-cervical region that developed after phlebotomy performed at the referring veterinarian's clinic. Ultrasound examination of the mass revealed a cystic structure in communication with the left carotid artery, with bidirectional blood flow through the area. A diagnosis of pseudoaneurysm secondary to accidental needle penetration of the carotid artery during jugular venepuncture was made. OUTCOME: Strict cage rest and pain management resulted in complete resolution of clinical and ultrasonographic signs in this cat.

Comparison of urine dipstick, sulfosalicylic acid, urine protein-to-creatinine ratio and a feline-specific immunoassay for detection of albuminuria in cats with chronic kidney disease.

The performance of the urine dipstick, sulfosalicylic acid (SSA), and urine protein-to-creatinine (UPC) tests for the detection of albuminuria was assessed in cats with chronic kidney disease (CKD). Two hundred and thirty-nine urine samples from 37 cats with CKD were used. Test results were dichotomized as either positive or negative, compared with those for the feline-specific rapid urine albumin immunoassay and test performance variables calculated for each test. A positive urine dipstick (≥ trace) and positive SSA (≥ 5 mg/dl), positive SSA alone or ≥ 2+ urine dipstick alone were indicative of albuminuria. In these cases, protein quantification would be warranted if proteinuria/albuminuria is persistent. In the case of a negative urine dipstick result the addition of the SSA added little diagnostic value. Of the tests investigated, the single best test for the detection of albuminuria was the UP/C (≥ 0.2) in which either a negative or positive test result provided useful information.

Renal transitional-cell carcinoma in two cats with chronic kidney disease.

Two 12-year-old cats were diagnosed with chronic kidney disease (CKD) based on physical examination, clinicopathologic data and, in one case, abdominal ultrasound findings. Approximately 1 year after the initial diagnosis of CKD both cats developed renal transitional cell carcinoma (TCC)--bilateral in one cat. Based on post-mortem examination, one cat had no evidence of metastasis and the other had metastasis to the large intestine, heart and lungs. This is the first report of de novo bilateral renal TCC in a cat, as well as the first report of renal TCC developing in cats with previous history of confirmed CKD.

Factors that influence the decision to pursue an internship: the importance of mentoring.

The purpose of the present study was (1) to determine if students from one veterinary school who participated in a mentoring/employment program with clinical faculty were more likely to pursue internship training than their peers and (2) to determine factors via survey that were influential to veterinary interns in making their decision to pursue post-graduate clinical training. Our hypothesis was that a mentoring relationship with clinical faculty was an important influence on the decision to participate in an internship. From 2006 to 2010, graduating students who participated in a mentoring/employment program with a clinical faculty member were 6.3 times more likely than non-participating students to pursue an internship. The majority of the participating students (90%) were initially hired/mentored as first- or second-year veterinary students. In the survey, interns ranked clinical faculty as having a greater influence than basic science faculty, private practice veterinarians, or house officers on their decision to pursue an internship; 82.8% reported that clinical faculty were most responsible for encouraging them to apply for an internship. Employment by their veterinary teaching hospital (41.5%) or directly by clinical faculty (26.2%) was commonly reported. Most interns (37%) decided to pursue an internship during their fourth year of veterinary school, 29.2% decided during their first year, and 15.3% decided in their second year. These results suggest that clinical faculty play a key role in a student's decision to pursue an internship and that it might be valuable to inform students about internships early in the veterinary curriculum.

Proteinuria: measurement and interpretation.

Proteinuria is a general term that describes the presence of any type of protein in the urine (e.g., albumin, globulins, mucoproteins, and Bence-Jones proteins); however, albumin is the predominate protein in urine in healthy dogs and cats as well as dogs and cats with renal disease. Proteinuria can arise from several different physiologic and pathologic causes, but persistent proteinuria associated with normal urine sediment is consistent with kidney disease. The urine dipstick colorimetric test is the usual first-line screening test for the detection of proteinuria, but false-positive reactions are common. When proteinuria of renal origin is suspected, the next diagnostic steps are quantitation and longitudinal monitoring via the urine protein/creatinine ratio. The recent availability of a species-specific albumin enzyme-linked immunosorbent assay technology that enables detection of low concentrations of canine and feline albuminuria has both increased diagnostic capability and stimulated discussion about what level of proteinuria/albuminuria is normal. Beyond being an important diagnostic marker, proteinuria is associated with kidney disease progression in both dogs and cats: the greater the magnitude of the proteinuria, the greater the risk of renal disease progression and mortality. Treatments that have attenuated proteinuria in dogs and cats have also been associated with slowed kidney disease progression and/or improved survival. For these reasons, screening for renal proteinuria and longitudinal assessment of renal proteinuria has recently received renewed interest.

Comparison of urine dipstick, sulfosalicylic acid, urine protein-to-creatinine ratio, and species-specific ELISA methods for detection of albumin in urine samples of cats and dogs.

OBJECTIVE: To evaluate the use of dipstick, sulfosalicylic acid (SSA), and urine protein-to-creatinine ratio (UP:C) methods for use in detection of canine and feline albuminuria. DESIGN: Evaluation study. SAMPLE POPULATION: 599 canine and 347 feline urine samples. PROCEDURES: Urine was analyzed by use of dipstick, SSA, and UP:C methods; results were compared with those for a species-specific ELISA to determine sensitivity, specificity, positive predictive value (PPV), negative predictive value, and positive and negative likelihood ratios. RESULTS: Positive results for dipstick and SSA tests (trace reaction or greater) in canine urine had moderate specificity (dipstick, 81.2%; SSA, 73.3%) and poor PPV (dipstick, 34.0%; SSA, 41.8%). Values improved when stronger positive results (>or= 2+) for the dipstick and SSA tests were compared with ELISA results (specificity, 98.9% and 99.0% for the urine dipstick and SSA tests, respectively; PPV, 90.7% and 90.2% for the dipstick and SSA tests, respectively). Data obtained for cats revealed poor specificity (dipstick, 11.0%; SSA, 25.4%) and PPV (dipstick, 55.6%; SSA, 46.9%). Values improved slightly when stronger positive test results (>or= 2+) were used (specificity, 80.0% and 94.2% for the dipstick and SSA tests, respectively; PPV, 63.5% and 65.2% for the dipstick and SSA tests, respectively). The UP:C had high specificity for albuminuria in dogs and cats (99.7% and 99.2%, respectively) but low sensitivity (28.7% and 2.0%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Caution should be used when interpreting a positive test result of a dipstick or SSA test for canine or feline albuminuria.

Comparison of student performance after lecture-based and case-based/problem-based teaching in a large group.

The purpose of this study was to compare traditional lecture-based (LB) and case-based/problem-based (CB/PB) learning in a large group. Year 3 veterinary students at Kansas State University were asked to participate in a randomized controlled study. Students were grouped and randomly assigned to be taught by a CB/PB or a LB method. Students took identical multiple-choice examinations, one given within a week of the last class and a different one given four months later. There was no direct effect of teaching method on group scores for either examination. CB/PB students scored higher on higher-difficulty questions on the first examination (p < 0.003), but there was no effect on questions of lower and medium difficulty. There was no effect of teaching method on student performance for the second examination; however, the question difficulty category scores were all different (p < 0.017). Evaluation of examination scores suggests that the two teaching methods were of similar efficacy.

Measurement, interpretation, and implications of proteinuria and albuminuria.

Proteinuria is a common disorder in dogs and cats that can indicate the presence of chronic kidney disease (CKD) before the onset of azotemia or the presence of more severe CKD after the onset of azotemia. Although a direct pathogenetic link between glomerular disease, proteinuria, and progressive renal damage has not been established, attenuation of proteinuria has been associated with decreased renal functional decline in several studies. There is a need to continue to increase our understanding of the effects of proteinuria on the glomerulus, the tubule, and the interstitium in dogs and cats.

Renal biopsy: a retrospective study of methods and complications in 283 dogs and 65 cats.

Renal biopsy often is required to establish a definitive diagnosis in dogs and cats with renal disease. In this retrospective study, we determined the complications of renal biopsy as well as factors that may be associated with development of complications and procurement of adequate renal biopsy specimens in 283 dogs and 65 cats. Data extracted from medical records at 4 institutions were evaluated using logistic regression. Proteinuria was the most common indication for renal biopsy in dogs. Complications were reported in 13.4 and 18.5% of dogs and cats, respectively. The most common complication was severe hemorrhage; hydronephrosis and death were uncommon. Dogs that developed complications after renal biopsy were more likely to have been 4 to < 7 years of age and > 9 years, to weigh < or = 5 kg, and to have serum creatinine concentrations > 5 mg/dL. The majority of biopsies from both dogs (87.6%) and cats (86.2%) were considered to be of satisfactory quality. Biopsies from dogs were more likely to be of high quality if they were obtained when the patient was under general anesthesia and more likely to contain only renal cortex if they were obtained by surgery. We concluded that renal biopsy is a relatively safe procedure, with a low frequency of severe complications. Hospital practices and patient variables have the potential to impact both the quality of the specimen obtained and the rate of complications.

Recruiting faculty with clinical responsibilities: factors that influence a decision to accept an academic position.

The current opportunities for veterinary clinical specialists in private practice and industry have made recruiting and retaining faculty a major focus for most clinical academic departments. To gain a better understanding of the importance of the various factors considered in accepting an academic position, an electronic survey was distributed to newly hired veterinary faculty with clinical responsibilities. The results suggest that the perceived climate and collegiality within the prospective hiring department is the most important factor influencing the decision to accept an academic position. Salary is the second most important factor. Institutional support for the newly hired faculty member and the reputation and quality of the prospective institution rank as more important than the perceived quality of the local community and the geographic location of the institution. The search process and administrative support are the least important factors. There were no differences between the responses of faculty hired into tenure-track positions and those of faculty hired into clinical-track positions. Focusing on the advantages of a collegial environment, enhancing compensation packages, and using creative and flexible appointments may improve faculty recruitment and retention in clinical academic departments.