Diet modulates proteinuria in heterozygous female dogs with X-linked hereditary nephropathy

Young adult heterozygous (carrier) female dogs with X-linked hereditary nephropathy (XLHN) have glomerular proteinuria but are otherwise healthy. Because data regarding dietary influences on the magnitude of proteinuria in dogs with spontaneous glomerular disease are not available, 12 such dogs were studied in a double crossover experiment intended to determine effects of altering dietary protein intake for up to 6 weeks. Dogs were blocked by urine protein : creatinine ratio (UPC) and randomly assigned to receive 2 diets: high protein (34.6% dry matter [DM], HP) or low protein (14.1% DM, LP) fed in HP-LP-HP or LP-HP-LP sequence. Food intake was measured daily, body weight (BW) was measured twice weekly, and UPC, plasma creatinine, blood urea nitrogen, phosphorus, albumin, and protein concentrations were measured at 2-week intervals. Nutrient digestibility was measured during the third treatment period. Diet had a significant effect (P < .0001) on all measured variables except plasma phosphorus (P > .5), but unintended differences in digestibility of protein and energy (P < or = .01) prevented assignment of the diet effect exclusively to protein. Proteinuria was greater (UPC 4.7 +/- 2.2 versus 1.8 +/- 1.1, P < .0001) when the HP diet was fed, but the LP diet did not maintain starting BW or plasma albumin concentration within the normal reference range. Diet greatly affects the magnitude of proteinuria in XLHN carrier females. Dietary protein restriction can reduce proteinuria in dogs with glomerular disease, but BW and blood protein concentrations may not be maintained if the restriction is too severe.     

Pathological features of proteinuric nephropathy resembling Alport syndrome in a young Pyrenean Mountain dog

The renal biopsy tissue from a 9-month-old, male Pyrenean Mountain dog with renal disorder and severe proteinuria was examined. Ultrastructural examination revealed multilaminar splitting and fragmentation of the glomerular basement membrane (GBM) and diffuse podocyte foot process effacement. Immunofluorescent staining for α(IV) chains revealed presence of α5(IV) and complete absence of α3(IV) and α4(IV) chains in the GBM. Immunohistochemistry also revealed decreased and altered expression of nephrin and podocin in the glomeruli compared with normal canine glomeruli. These results suggested that the glomerular disease of the present case might be consistent with canine hereditary nephropathy resembling human Alport syndrome caused by genetic defect of type IV collagen, and indicated possible contribution of podocyte injury to severe proteinuria in this case.     

A gonioscopic study of the iridocorneal angle in the English and American breeds of Cocker Spaniel and the Basset Hound

Closure of the iridocorneal angle is the cause of a primary form of glaucoma which occurs in certain breeds of dog, but the precise mechanism involved in that closure is not completely understood. However, narrowness of the angle is considered to be the important predisposing factor, and in gonioscopic survey work the author has demonstrated that angle narrowness occurs with some frequency in the English Cocker Spaniel and Basset Hound breeds.     

Characterization of chronic pancreatitis in English Cocker Spaniels

Background: Chronic pancreatitis (CP) is common in dogs. The cause is unknown. In humans, different causes of pancreatitis have histologically distinct appearances. The histopathologic lesions in English Cocker Spaniels (ECS) with CP were noted to be histologically different than those of other breeds with CP. Hypothesis: CP in ECS is distinct from CP in other breeds and is characterized by a duct destruction similar to what is observed in autoimmune CP of humans. Animals: Eight ECS and 9 other breeds with histologically confirmed CP recruited over an 8‐year period and 50 postmortem control dogs with CP. Methods: Clinical, clinicopathological, and ultrasonographic findings were recorded. Histological sections were compared with a normal dog and 59 dogs of other breeds with CP. Immunohistochemistry using anti‐CD3, anti‐CD79a, and anti‐cytokeratin antibodies was used to evaluate distribution and type of lymphocytic inflammation and appearance of pancreatic ducts. Results: Four male and 4 female ECS presented at a mean age of 7.2 years. Clinical signs were similar in ECS and other breeds. The pancreas was enlarged and hypoechoic in 4 ECS and 2 controls. Histopathology was characterized by interlobular and periductular fibrosis and inflammation in ECS compared with intralobular disease in most other breeds. Immunohistochemistry identified prominent anti‐CD3⁺ lymphocytic infiltrates around venules and ducts and a marked absence of interlobular ducts in ECS compared with mixed T‐cell infiltration and ductular hyperplasia in most other breeds with CP. Conclusions and Clinical Importance: CP in ECS is distinct from CP in other breeds and is notably duct destructive.     

Diagnosis of pneumocystis pneumonia in a 2‐year‐old King Charles Cavalier Spaniel using the polymerase chain reaction

A 2‐year‐old, female spayed, King Charles Cavalier Spaniel was presented for evaluation of dyspnea, inappetence, and lethargy. Thoracic radiographs revealed a moderate diffuse interstitial lung pattern affecting the perihilar and caudodorsal lung fields, and an echocardiogram revealed severe pulmonary hypertension. A bronchoalveolar lavage (BAL) was performed, and cytology revealed mixed inflammation with cysts and trophozoites consistent with Pneumocystis. Pneumocystis infection was later confirmed with PCR. To the author's knowledge, this report represents the first case of canine pneumocystis pneumonia diagnosed antemortem with PCR from a BAL sample. Pneumocystis represents an important, but uncommon cause of afebrile pneumonia in immunosuppressed dogs.     

Genetic Analysis of Ventricular Arrhythmia in Young German Shepherd Dogs

Background: Ventricular arrhythmias (VA) and sudden death are inherited in German Shepherd Dogs (GSDs).
Objectives: To estimate the genetic parameters (heritabilities and correlations) of 3 traits of VA (single premature ventricular complexes (PVCs), 2 consecutive PVCs (couplets), and 3 or more consecutive PVCs—ventricular tachycardia [VT]).
Animals: Three hundred and ninety-eight GSDs.
Methods: Prospective, observational, case control study. Dogs were phenotyped by 24-hour ambulatory ECG from 6 to 45 weeks of age. Edited ECG records included the number of incidents of (1) single PVCs, (2) couplets, and (3) VT.
Results: A data set of 1,239 Holter records from 398 GSDs was used to estimate genetic variables. Phenotypic correlations for affectedness (binarily coded 0/1) of the 3 traits ranged from 0.55 to 0.74, whereas correlations for severity (continuous values of 24-hour VA counts) ranged from 0.26 to 0.39. Estimates of genetic correlation among the severity traits were 0.06 to 0.27. Estimated heritabilities were 0.54, 0.54, and 0.46 for affectedness and 0.33, 0.69, and 0.69 for severity of PVCs, couplets, and VT, respectively. Month and year of birth and age at ECG recording had significant effects on all 3 traits. Season of ECG recording had a significant effect on the number of single PVCs, but not couplets or incidents of VT. Age of onset differed, with single PVCs appearing an average of 4 days earlier than couplets and VT.
Conclusion: These results imply a strong genetic component for this disease but suggest that differences in the 3 traits should be taken into consideration in studies to identify the underlying genes.     

Pectinate ligament dysplasia and narrowing of the iridocorneal angle associated with glaucoma in the English Springer Spaniel

Objective The aim of the study was to evaluate if tonometry and gonioscopy could serve as predictors of later glaucoma development in the English Springer Spaniel, a breed prone to developing primary glaucoma. Animals studied Gonioscopy was performed on 279 English Springer Spaniel dogs, 119 males and 160 females, with clinically normal eyes. In addition, 14 dogs, five males and nine females were examined for glaucoma. Results A positive relation between pectinate ligament dysplasia (PLD) and narrowing of the relative width of the ciliary cleft (RWOCC) and also between PLD, RWOCC and age was demonstrated. The prevalence of PLD was 25.5%, which is higher than in other breeds reported. A positive association was demonstrated between PLD and glaucoma, as well as between narrowing of the RWOCC and glaucoma. Glaucoma was not observed in dogs with normal appearance of the iridocorneal angle. English Springer Spaniels related to dogs with glaucoma show more narrowing of the RWOCC and more PLD than unrelated dogs. Conclusion This study demonstrates the positive association between PLD and glaucoma, between narrowing of the iridocorneal angle and glaucoma and the effect of age on the iridocorneal angle. Mating of dogs with normal iridocorneal angles appears to reduce the presence and degree of abnormal appearance of the iridocorneal angle in the offspring. However, breeding only dogs with normal iridocorneal angles without consideration of their relationship to dogs with glaucoma is not a guarantee for preventing glaucoma in the offspring.     

Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug

Necrotizing meningoencephalitis (NME) in the Pug is an invariably fatal disease with an early age of onset whose cause remains unknown. Breed predilection strongly suggests genetic component(s), and viral etiology proves negative in studied cases. The current study was undertaken as the first analysis of the heritable component(s) involved in NME in the Pug. Complete medical records, individual characteristics, and pedigree information were collected for 58 affected dogs with data pertaining to 4698 dogs analyzed. A high inbreeding coefficient with differences across gender and significant differences across coat color classes and variable expression was evident. Median onset age was 19 months and median survival time 23 days. Screening for herpes-, adeno-, and parvoviruses was negative. The data demonstrate a strong familial inheritance of NME in the Pug. This investigation provides parameters of disease from the largest Pug NME cohort analyzed to date and offers evidence of previously unrecognized familial inheritance.     

Day-to-Day variation of the urine protein: creatinine ratio in female dogs with stable glomerular proteinuria caused by X-linked hereditary nephropathy

BACKGROUND: Interpretation of serial urine protein:creatinine (UPC) values is confounded by a lack of data regarding random biologic variation of UPC values in dogs with stable glomerular proteinuria. HYPOTHESIS: That there is minimal day-to-day variability in the UPC of dogs with unchanging proteinuria and the number of measurements needed to reliably estimate UPC varies with the magnitude of proteinuria. ANIMALS: Forty-eight heterozygous (carrier) female dogs with X-linked hereditary nephropathy (XLHN) causing stable proteinuria. METHODS: Urine samples were obtained daily by cystocentesis for 3 consecutive days on 183 occasions (549 samples). The UPC was measured for each sample with a single dry-film chemistry auto-analyzer. Data were analyzed retrospectively by a power of the mean model because the variance of UPC values within the 3-day evaluation periods increased as the magnitude of proteinuria increased. RESULTS: To demonstrate a significant difference (P < .05) between serial values in these proteinuric dogs, the UPC must change by at least 35% at high UPC values (near 12) and 80% at low UPC values (near 0.5). One measurement is adequate to reliably estimate the UPC when UPC <4, but 2-5 determinations are necessary at higher UPC values. CONCLUSIONS AND CLINICAL IMPORTANCE: These guidelines for interpretation of serial UPC values in female dogs with XLHN may also be helpful for interpretation of UPC values in dogs with other glomerulopathies.     

Retrospective comparison of the efficacy of fluconazole or itraconazole for the treatment of systemic blastomycosis in dogs

Background: Itraconazole is recommended for treatment of blastomycosis in dogs. Some evidence suggests that fluconazole might be less hepatotoxic than itraconazole. Objectives: To compare (1) incidence of clinical remission and death; (2) treatment duration; (3) total drug cost; (4) incidence of relapse; and (5) incidence of increased ALT activities in dogs with blastomycosis treated with fluconazole or itraconazole. Animals: One hundred and forty‐four dogs with systemic blastomycosis treated with itraconazole or fluconazole from 1998 to 2008. Methods: Retrospective case review. Information obtained included signalment, body weight, clinical signs, drug regimen, treatment duration, time to clinical remission, and laboratory results. Results: Neither treatment efficacy between fluconazole (75% remission) and itraconazole (90% remission) nor relapse rate (18% for itraconazole, 22% for fluconazole) was significantly different (P= .13, .75, respectively). Treatment duration was significantly longer for fluconazole (median 183 days) than for itraconazole (138 days; P= .001). Costs for fluconazole (median $1,223) were significantly less than for itraconazole ($3,717; P < .001). Incidence of increased ALT activities was not significantly different between groups (17% [3/18] for fluconazole, 26% [6/23] for itraconazole; P= .71). Conclusions: Fluconazole is associated with survival to clinical remission in 75% of dogs with blastomycosis. Although dogs receiving fluconazole were treated longer, drug costs were one‐third those of itraconazole. Hepatotoxicosis, as estimated by increases in serum ALT activity, can be observed with similar incidence for both drugs.     

A retrospective study on the prevalence of primary cataracts in two pedigrees from the German population of English Cocker Spaniels

Objective  Two pedigrees from the German English Cocker Spaniel population are presented to illustrate the familial occurrence of primary cataract (CAT) in single- and multicolored English Cocker Spaniels. The aim was to characterize similarities and differences in the prevalence and formation of CAT in these separately bred color variants of English Cocker Spaniels.
Materials  The study was based on the veterinary records for presumed inherited eye diseases of 1232 English Cocker Spaniels which were provided by the German panel of the European Eye Scheme for diagnosis of inherited eye diseases in animals (DOK, < http://www.dok-vet.de >). Data included information on 615 single-colored and 617 multicolored English Cocker Spaniels.
Results  CAT was diagnosed in 92 (14.96%) of the single-colored and 34 (5.51%) of the multicolored English Cocker Spaniels. The pedigree of the single-colored English Cocker Spaniels included 40 ophthalmologically examined dogs with 18 unaffected and 22 affected dogs. The pedigree of the multicolored English Cocker Spaniels contained 16 ophthalmologically examined dogs with 11 unaffected and five affected dogs.
Conclusions  In both color variants of the English Cocker Spaniels different forms of primary CAT with respect to location within the lens occurred among close relatives. Appearance of CAT was very heterogeneous without obvious sex differences. The sample pedigrees do not support the assumption of familial segregation of specific forms of primary CAT in English Cocker Spaniels.     

西藏牦牛血清乳酸脱氢酶H亚基的遗传变异体

采用聚丙烯酰胺凝胶电泳分析西藏嘉黎和亚东地区８５头牦牛血清乳酸脱氢酶（ＬＤＨ）同工酶。结果显示，牦牛血清ＬＤＨ同工酶具有ＬＤＨ１￣ＬＤＨ５五种形式，ＬＤＨ的Ｈ亚基存在Ａ、Ｂ、Ｃ三种遗传变异体，Ｃ型遗传变异体平均占８２．３５％。值得注意的是，嘉黎地区具有Ａ或Ｂ型Ｈ亚型的牦牛血清中ＬＤＨ２的相对活力显著低于具有Ｃ型Ｈ亚基的牦牛，其机制和意义有待进一步研究。     

Stenting of the right ventricular outflow tract in 2 dogs for palliation of dysplastic pulmonary valve stenosis and right-to-left intracardiac shunting defects

Two dogs with severe dysplastic pulmonary valve stenosis and right-to-left shunting defects (patent foramen ovale, perimembranous ventricular septal defect) underwent palliative stenting of the right ventricular outflow tract and pulmonary valve annulus using balloon expandable stents. One dog received 2 over-lapping bare metal stents placed 7 months apart; the other received a single covered stent. Both procedures were considered technically successful with a reduction in the transpulmonary valve pressure gradient from 202 to 90 mmHg in 1 dog and from 168 to 95 mmHg in the other. Clinical signs of exercise intolerance and syncope were temporarily resolved in both dogs. However, progressive right ventricular concentric hypertrophy, recurrent stenosis, and erythrocytosis were observed over the subsequent 6 months leading to poor long-term outcomes. Stenting of the right ventricular outflow tract is feasible in dogs with severe dysplastic pulmonary valve stenosis, though further study and optimization of the procedure is required.