Shelly L. Vaden

Effects of enalapril versus placebo as a treatment for canine idiopathic glomerulonephritis.

A blinded, multicenter, prospective clinical trial assessed the effects of enalapril (EN) versus standard care in dogs with naturally occurring, idiopathic glomerulonephritis (GN). Twenty-nine adult dogs with membranous (n = 16) and membranoproliferative (n = 13) GN were studied. Dogs were randomly assigned to receive either EN (0.5 mg/kg PO q12-24h; n = 16) or placebo (n = 14) for 6 months (1 dog was treated first with the placebo and then with EN). All dogs were treated with low-dose aspirin (0.5-5 mg/kg PO q12-24h) and fed a commercial diet. At baseline, serum creatinine (SrCr), systolic blood pressure (SBP), and glomerular histologic grade were not different between groups, but the urine protein/creatinine ratio (UP/C) was greater in the EN group compared with the placebo group (8.7 +/- 4.4 versus 4.7 +/- 2.3). After 6 months of treatment, the change in UP/C from baseline was significantly different between groups (EN = -4.2 +/- 1.4 versus 1.9 +/- 0.9 in the placebo group). When data were adjusted for changes in SrCr (SrCr X UP/C) a similar significant reduction was noted ( 2.2 +/- 15.2 versus 8.4 +/- 10.1). The change in SBP after 6 months of treatment also was significantly different between groups (EN = -12.8 +/- 27.3 versus 5.9 +/- 21.5 mm Hg in the placebo group). Response to treatment was categorized as improvement (assigned a value of 2), no progression (assigned a value of 1), and progression (assigned a value of 0). Response was significantly better in the EN group (1.4 +/- 0.8) compared with the placebo group (0.3 +/- 0.5). These results suggest that EN treatment is beneficial in dogs with naturally occurring idiopathic GN.

Familial Protein‐Losing Enteropathy and Protein‐Losing Nephropathy in Soft Coated Wheaten Terriers: 222 Cases (1983–1997)

Records and pedigrees of Soft Coated Wheaten Terriers (SCWT) with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) were studied retrospectively. Criteria for inclusion were defined based on analysis of blood (panhypoproteinemia for PLE, hypoalbuminemia for PLN) and urine (proteinuria for PLN) and histopathologic examination of tissue. Two hundred twenty-two affected dogs (female:male ratio = 1.6, P < .001) were clinically identified. Dogs were diagnosed with PLE earlier (P < .005; mean +/- SD age: 4.7+/-2.6 years, n = 76) than with PLN (6.3+/-2.0 years, n = 84) or with both diseases (5.9+/-2.2 years, n = 62). Clinical signs included vomiting, diarrhea, weight loss, pleural and peritoneal effusions, and less commonly thromboembolic disease. Dogs with PLE generally had panhypoproteinemia and hypocholesterolemia; intestinal lesions included inflammatory bowel disease, dilated lymphatics, and lipogranulomatous lymphangitis. Dogs with PLN generally had hypoalbuminemia, proteinuria, hypercholesterolemia, and azotemia; renal lesions typically showed chronic glomerulonephritis/glomerulosclerosis, and less commonly endstage renal disease. Dogs with combined PLE/PLN had intermediate mean values (P < .001) for serum total protein, albumin, globulin, and cholesterol but had a higher mean urine protein:creatinine ratio than did PLN dogs (P < .05); intestinal and renal lesions in these dogs were similar to those in the other groups. Two dogs had incidental mild renal dysplasia. Pedigree analysis from 188 dogs demonstrated a common male ancestor, although the mode of inheritance is unknown. Both PLE and PLN are common diseases in this small breed population. The prognosis is poor. Compared with previously reported intestinal and renal diseases in dogs, a new, distinctive familial predisposition for both PLE and PLN has been recognized in the SCWT breed.

Hypercalcemia in Cats: A Retrospective Study of 71 Cases (1991–1997)

A retrospective study was conducted to characterize the diseases, clinical findings, and clinicopathologic and ultrasonographic findings associated with hypercalcemia (serum calcium concentration >11 mg/dL) in 71 cats presented to North Carolina State University Veterinary Teaching Hospital. The 3 most common diagnoses were neoplasia (n = 21), renal failure (n = 18), and urolithiasis (n = 11). Primary hyperparathyroidism was diagnosed in 4 cats. Lymphoma and squamous cell carcinoma were the most frequently diagnosed tumors. Calcium oxalate uroliths were diagnosed in 8 of 11 cats with urolithiasis. Cats with neoplasia had a higher serum calcium concentration (13.5 +/- 2.5 mg/dL) than cats with renal failure or urolithiasis and renal failure (11.5 +/- 0.4 mg/dL; P < .03). Serum phosphorus concentration was higher in cats with renal failure than in cats with neoplasia (P < .004). Despite the fact that the majority of cats with uroliths were azotemic, their serum urea nitrogen and creatinine concentrations and urine specific gravity differed from that of cats with renal failure. Additional studies are warranted to determine the underlying disease mechanism in the cats we identified with hypercalcemia and urolithiasis. We also identified a small number of cats with diseases that are not commonly reported with hypercalcemia. Further studies are needed to determine whether an association exists between these diseases and hypercalcemia, as well as to characterize the underlying pathophysiologic mechanism for each disease process.

Candida spp. Urinary Tract Infections in 13 Dogs and Seven Cats: Predisposing Factors, Treatment, and Outcome

Records from 20 animals (13 dogs, seven cats) with Candida spp. urinary tract infections were reviewed. Six Candida spp. were isolated; Candida albicans was the most common isolate. Concurrent diseases or nonantifungal drugs administered within 1 month of isolation included antibiotics (n=16), corticosteroids (n=6), diabetes mellitus (n=4), nonurogenital neoplasia (n=3), and noncandidal urogenital disease (n=14). All animals had sources of local or systemic immune compromise that likely predisposed to infection. Of five animals with resolution of infection, three did not receive specific antifungal treatment. The authors conclude that correction of predisposing conditions is likely critical for management of Candida spp. urinary tract infection.

Prevalence and classification of chronic kidney disease in cats randomly selected from four age groups and in cats recruited for degenerative joint disease studies

Chronic kidney disease (CKD) and degenerative joint disease are both considered common in older cats. Information on the co-prevalence of these two diseases is lacking. This retrospective study was designed to determine the prevalence of CKD in two cohorts of cats: cats randomly selected from four evenly distributed age groups (RS group) and cats recruited for degenerative joint disease studies (DJD group), and to evaluate the concurrence of CKD and DJD in these cohorts. The RS group was randomly selected from four age groups from 6 months to 20 years, and the DJD group comprised cats recruited to four previous DJD studies, with the DJD group excluding cats with a blood urea nitrogen and/or serum creatinine concentration >20% (the upper end of normal) for two studies and cats with CKD stages 3 and 4 for the other two studies. The prevalence of CKD in the RS and DJD groups was higher than expected at 50% and 68.8%, respectively. CKD was common in cats between 1 and 15 years of age, with a similar prevalence of CKD stages 1 and 2 across age groups in both the RS and DJD cats, respectively. We found significant concurrence between CKD and DJD in cats of all ages, indicating the need for increased screening for CKD when selecting DJD treatments. Additionally, this study offers the idea of a relationship and causal commonality between CKD and DJD owing to the striking concurrence across age groups and life stages.

Modulation of doxorubicin concentration by cyclosporin A in brain and testicular barrier tissues expressing P-glycoprotein in rats.

P-glycoprotein (Pgp) is an inducible transmembrane protein that functions as an ATP-dependent efflux pump. Pgp is normally expressed in two types of cells: specialized epithelial cells with secretory/excretory functions (e.g., proximal renal tubules) and specialized endothelial cells (e.g., the capillary endothelial cells of the blood-brain barrier). In normal tissues, Pgp could exert a cytoprotective effect by facilitating excretion of drugs. It follows that inhibition of Pgp would alter the pharmacokinetics of drugs, like doxorubicin, in cells that express Pgp. The purpose of this study was to determine whether or not inhibition of Pgp by cyclosporin A (CsA) facilitated the transport of certain drugs across the blood tissue barriers of the brain and testes (barriers tissues expressing Pgp). 120 retired male breeder CD Fisher rats were randomly assigned to groups of 4 rats each. They were given either CsA, CsA vehicle, or saline followed by doxorubicin (Dox), cisplatin (CDDP), Evans blue (EB), sodium fluorescein (NaF), or horseradish peroxidase (HRP). There was a CsA dose dependent increase in the tissue concentration of doxorubicin in brain and testes, but platinum (Pt) concentrations, derived from CDDP, were unaffected. Unlike CDDP, Dox, can be effluxed by Pgp. These increases in Dox concentrations were not due to altered vascular permeability as a result of CsA treatment as determined by lack of EB, NaF, or HRP in brain parenchyma. Modulation of Pgp function may prove to be useful for improving chemotherapy efficacy for patients with malignancies affecting tissues with blood-tissue barriers.

Auto IgG anti-IgE and IgG × IgE immune complex presence and effects on ELISA-based quantitation of IgE in canine atopic dermatitis, demodectic acariasis and helminthiasis

Atopic dermatitis is a common allergic disease manifestation in dogs; however, there is no correlation between clinical disease and detectable total serum IgE. Auto antibodies of the IgG subclass against IgE may affect the detection of serum IgE by immunoassay and may be important in the regulation of IgE production by B cells. ELISA were developed to detect serum antibodies specific for IgE using a newly available canine monoclonal IgE of known antigen specificity, generated from a canine x murine heterohybridoma. To test for correlation of auto IgG anti-IgE levels with manifestation of atopic dermatitis, the sera from 101 atopic dogs were compared with sera from non-atopic dogs of various breeds, foxhounds manifesting clinical signs of demodectic acariasis and helminth parasitized random bred dogs for quantities of IgG anti-IgE measured in units/ml compared to a high titer standard serum. To test for serum effects on quantitation of IgE, known amounts of canine monoclonal IgE were added to various sera and measured by capture ELISA with detecting monoclonal antibodies specific for heat labile or heat stabile epitopes. Unheated sera from dogs manifesting clinical atopic dermatitis and helminth parasitized dogs had levels of IgG anti-IgE that were significantly lower than various breeds of dogs not manifesting dermatologic lesions and foxhounds manifesting demodectic acariasis. Heating sera at 56 degrees C for 3 h to denature the high affinity binding site on the IgE heavy chain caused a marked increase over non-heated sera in detectable IgG anti-IgE in almost all dogs. This increase was most profound in helminth-infected dogs and foxhounds manifesting demodectic mange with 7 fold increases each, respectively, and in atopic dogs with a 5 fold increase compared to 3 fold increases for clinically-normal springer spaniels and all soft coated wheaten terriers. The terriers demonstrated an association of lower heated serum values of IgG anti-IgE with manifestation of a familial syndrome of protein-losing enteropathy and protein-losing nephropathy. The ability of mouse anti-canine IgE monoclonal antibodies specific for either heat labile or heat stabile epitopes to detect canine monoclonal IgE added to sera in known amounts varied from serum to serum and at different concentrations of the same serum, but did not correlate with IgG anti-IgE values for these sera. The range of absolute levels of serum IgE in dogs showing little or no inhibition of detection of added IgE was < 0.5 ng/micromilligram to 2 micrograms/micromilligram. It was concluded that the increase in detectable IgG anti-IgE after heating sera indicates that IgG x IgE immune complexes are normally present in most dogs; however, the increase over uncomplexed IgG anti-IgE was most pronounced in dogs manifesting atopic dermatitis and demodectic acariasis. A quantitative comparison of IgG anti-IgE or IgG x IgE to total serum IgE was not made because the ability of monoclonal antibodies specific for either heat labile or heat stable epitopes on the IgE heavy chain to detect IgE added to serum, as well as innate serum IgE, was highly variable in different dilutions of serum from individual to individual.

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.

Prevalence of Urinary Tract Infection in Dogs after Surgery for Thoracolumbar Intervertebral Disc Extrusion

BACKGROUND Urinary tract infection (UTI) is a common complication in people with spinal cord injury (SCI). Dogs with acute intervertebral disc extrusion (IVDE) have similar risk factors for UTI when compared with human SCI patients and have a high perioperative prevalence of UTI. OBJECTIVES Determine the prevalence of UTI in dogs for 3 months after surgery for thoracolumbar IVDE and identify risk factors for development of UTI. ANIMALS Twenty-five dogs treated surgically for 26 acute disc extrusions. METHODS Prospective study. Urinalysis and urine culture were performed perioperatively. At home, owners monitored urine with dipsticks every 48 hours for 1 month then once a week until 3 months. Dogs returned for assessment of motor function, urinalysis, and urine culture at 1 and 3 months after surgery. Presence of UTI over the 3-month period was correlated to potential risk factors. RESULTS Ten dogs (38%) developed 12 UTIs over the 3-month period, with the majority occurring between weeks 1 and 6; 60% of the UTIs were occult. Hematuria in the absence of pyuria or UTI was a common finding in the perioperative period. Sex, breed, and ambulatory status influenced the risk of developing a UTI. CONCLUSIONS AND CLINICAL IMPORTANCE There is a high prevalence of UTIs, many of which are occult, in the 3 months after surgery for thoracolumbar IVDE. These dogs should be routinely monitored for UTI with urine culture regardless of urinalysis results.

Hypercoagulability in dogs with protein-losing nephropathy as assessed by thromboelastography.

BACKGROUND Dogs with protein-losing nephropathy (PLN) are at risk of thromboembolic disease, but the mechanism leading to hypercoagulability and the population of dogs at risk are unknown. OBJECTIVES To characterize thromboelastography (TEG) and its association with serum albumin (SALB), UPC, and antithrombin activity in dogs with PLN. ANIMALS Twenty-eight client-owned dogs with PLN (urine protein:creatinine ratio [UPC] > 2.0) and 8 control dogs were prospectively enrolled in this observational study. METHODS TEG parameters, antithrombin activity, serum biochemical profiles, and UPC were measured. TEG analyses were run in duplicate with kaolin activation; reaction time (R), clot formation time (K), α-angle (α), maximal amplitude (MA), and global clot strength (G) were analyzed. RESULTS Dogs with PLN had lower K (P = .004), and higher α (P = .001), MA (P < .001), and G (P < .001) values than controls. No significant correlation between TEG parameters and UPC, SALB, or antithrombin was noted. Twelve PLN dogs (42.8%) were azotemic and 19 (67.8%) were hypoalbuminemic (SALB < 3.0 g/dL); 11 had SALB < 2.5 g/dL. CONCLUSIONS AND CLINICAL IMPORTANCE These results indicate that dogs with PLN have TEG values that demonstrate hypercoagulability compared with a control population but that antithrombin, SALB, or UPC cannot be used in isolation to predict this result. A comprehensive evaluation of the coagulation system in individual patients may be necessary to predict the point at which anti-thrombotic therapy is indicated.