Renal pathology of polycystic kidney disease and concurrent hereditary nephritis in Bull Terriers

OBJECTIVE: To describe the renal lesions in Bull Terrier polycystic kidney disease (BTPKD), to confirm that the renal cysts in BTPKD arise from the nephron or collecting tubule, and to identify lesions consistent with concurrent BTPKD and Bull Terrier hereditary nephritis (BTHN). DESIGN: Renal tissue from five Bull Terriers with BTPKD and eight control dogs was examined by light and transmission electron microscopy. Clinical data were collected from all dogs, and family history of BTPKD and BTHN for all Bull Terriers. RESULTS: In BTPKD the renal cysts were lined by epithelial cells of nephron or collecting duct origin that were usually squamous or cuboidal, with few organelles. They had normal junctional complexes, and basal laminae of varying thicknesses. Glomeruli with small, atrophic tufts and dilated Bowman's capsules, tubular loss and dilation, and interstitial inflammation and fibrosis were common. Whereas the lesions seen in BTHN by light microscope were nonspecific, the presence of characteristic ultrastructural glomerular basement membrane (GMB) lesions and a family history of this disease indicated concurrent BTHN was likely in three of five cases of BTPKD. CONCLUSION: This paper provides evidence that renal cysts in BTPKD are of nephron or collecting duct origin. In addition, GBM lesions are described that strongly suggest that BTPKD and BTHN may occur simultaneously.     

Familial progressive nephropathy in young Bull Terriers

The clinical, clinicopathological and pathological findings are described in three Bull Terrier bitches with advanced renal disease. The bitches were less than four years old and showed variable presenting signs but anorexia, lethargy and polydipsia were the most frequent. All three dogs were azotaemic and isosthenuric. Urinary protein was measured in two of the three cases. Both were proteinuric. At necropsy all dogs had shrunken kidneys. Histological examination revealed nephron loss, atrophy of glomerular tufts, interstitial fibrosis, and mineralisation of basement membranes. The progressive renal disease in these dogs was similar to the condition reported in Bull Terriers in Australia, and is probably familial and inherited.     

Familial progressive nephropathy in young Bull Terriers

The clinical, clinicopathological and pathological findings are described in three Bull Terrier bitches with advanced renal disease. The bitches were less than four years old and showed variable presenting signs but anorexia, lethargy and polydipsia were the most frequent. All three dogs were azotaemic and isosthenuric. Urinary protein was measured in two of the three cases. Both were proteinuric. At necropsy all dogs had shrunken kidneys. Histological examination revealed nephron loss, atrophy of glomerular tufts, interstitial fibrosis, and mineralisation of basement membranes.

The progressive renal disease in these dogs was similar to the condition reported in Bull Terriers in Australia, and is probably familial and inherited.     

L-2-Hydroxyglutaric aciduria in Staffordshire Bull Terriers

L-2-Hydroxyglutaric aciduria is an inborn error of metabolism, which has been recognized in humans since 1980. The metabolic defect responsible for the disease is unknown, but the disorder can be diagnosed in humans by elevations of the organic acid, L-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF), plasma, and urine of affected patients. The disorder produces a variety of clinical neurological defects in humans including psychomotor retardation, seizures, and ataxia. There have previously been no recognized animal models of the disease. However, 6 Staffordshire Bull Terriers were recently identified with the disorder. The animals presented with a variety of clinical signs, most notably seizures, ataxia, dementia, and tremors. They were all screened for organic acid abnormalities in urine, and CSF and plasma (when available). Levels of L-2-hydroxyglutaric acid were elevated in all body fluids evaluated. The clinical, clinicopathologic, and magnetic resonance imaging (MRI) characteristics associated with L-2-hydroxyglutaric acid in Stafforshire Bull Terriers is reported herein and represents the first veterinary model of this inborn error of metabolism.     

Echocardiographic parameters in 14 healthy English Bull Terriers

OBJECTIVE: To determine the range of various cardiac parameters using echocardiography in apparently normal, healthy English Bull Terriers. DESIGN: Fourteen English Bull Terriers were selected for study. Cardiac auscultation of the parents of these dogs was normal. Echocardiographic examination of one parent of each animal showed: no mitral or aortic valve abnormalities; no myocardial lesions; no two dimensional evidence of fixed or dynamic left ventricular outflow tract obstruction; and no systolic aortic or left ventricular outflow tract turbulence on colour flow Doppler examination. The 14 selected dogs did not have arrhythmias or murmurs, and on echocardiographic examination had similar findings to their parents. Systolic blood pressure was measured in all dogs and they had no clinical evidence of Bull Terrier polycystic kidney disease or Bull Terrier hereditary nephritis. PROCEDURE: All dogs were auscultated and subjected to a sequential global echocardiographic assessment of the heart, including two dimensional long and short axis, and colour flow Doppler interrogation of the mitral and aortic valves. Dimensional measurements, including those from the left atrium, aortic annulus and left ventricle, were taken from a right parasternal window, and derived values such as fractional shortening, stroke volume and left atrial to aortic annulus ratio were calculated. Peak systolic aortic velocity was measured from the left parasternal window using two dimensional-guided pulsed wave Doppler with angle correction. Systolic blood pressure was measured using a Doppler monitor. The absence of Bull Terrier polycystic kidney disease was determined using renal ultrasonography, and of Bull Terrier hereditary nephritis using urinary protein to creatinine ratio. RESULTS: These 14 dogs had greater left ventricular wall thickness and smaller aortic root diameters than those reported as normal for other breeds of comparable body size. Left atrial dimensions were also larger, however this may have been due to the "maximising" method of measurement. These apparently normal English Bull Terriers also had higher aortic velocities than those reported for other breeds, possibly due to a smaller aortic root diameter or other anatomic substrate of the left ventricular outflow tract, lower systemic vascular resistance, or breed-specific "normal" left ventricular hypertrophy. While these dogs were selected to be as close to normal as possible, the breed may have a particular anatomy that produces abnormal left ventricular echocardiographic parameters. CONCLUSION: These echocardiographic parameters may be used to diagnose left ventricular outflow tract obstruction and left ventricular hypertrophy, and inaccurate diagnoses may result if breed-specific values are not used.     

Congenital polycystic kidney disease in lambs

AIM: To describe the pathology and inheritance of a congenital polycystic kidney disease (PKD) of sheep. METHODS: Mode of inheritance of PKD was investigated by evaluation of results of the disorder from planned matings in two consecutive years within subsets of a flock that had a high prevalence of PKD in lambs. Gross pathological and histopathological studies were based on tissues derived from this study. Haematoxylin and eosin (H&E)-stained paraffin sections of kidney, liver, extrahepatic biliary and pancreatic ducts, pancreas and epididymis were used to describe the lesions. RESULTS: Twenty-five lambs affected by PKD, of both sexes, were born, numbers in accord with those expected for an autosomal recessive disorder in the population studied. In all cases for which tissues were available, the renal, bile ductal (intrahepatic and extrahepatic), pancreatic and epididymal tissues had widespread dysplastic changes and associated cyst formation. CONCLUSIONS: The findings of renal cysts in conjunction with cysts in other organs are unifying features in many of the human and animal forms of PKD and suggest a related pathogenic and genetic base consistent with an autosomal recessive disorder.     

Congenital polycystic kidney disease in lambs

AIM: To describe the pathology and inheritance of a congenital polycystic kidney disease (PKD) of sheep.

METHODS: Mode of inheritance of PKD was investigated by evaluation of results of the disorder from planned matings in two consecutive years within subsets of a flock that had a high prevalence of PKD in lambs. Gross pathological and histopath- ological studies were based on tissues derived from this study. Haematoxylin and eosin (H&E)-stained paraffin sections of kidney, liver, extrahepatic biliary and pancreatic ducts, pancreas and epididymis were used to describe the lesions.

RESULTS: Twenty-five lambs affected by PKD, of both sexes, were born, numbers in accord with those expected for an autosomal recessive disorder in the population studied. In all cases for which tissues were available, the renal, bile ductal (intrahepatic and extrahepatic), pancreatic and epididymal tissues had widespread dysplastic changes and associated cyst formation.

CONCLUSIONS: The findings of renal cysts in conjunction with cysts in other organs are unifying features in many of the human and animal forms of PKD and suggest a related pathogenic and genetic base consistent with an autosomal recessive disorder.     

Lethal Acrodermatitis in Bull Terriers: A Problem of Defective Zinc Metabolism

Abstract— Three bull terrier pups from a litter of six developed exfoliative, crusty areas of alopecia, particularly affecting the feet and head, by the time they were seven weeks of age. Biopsies from two of the affected pups revealed parakeratotic hyperkeratosis consistent with zinc deficiency, but the dogs did not respond to oral zinc supplements. The breed, history and dermatopathology were considered consistent with lethal acrodermatitis of bull terriers, a condition that appears to be familial and autosomally recessive. Whereas similar acrodermatitic conditions in humans (acrodermatitis enteropathica) and cattle (lethal trait A46 of Black Pied Danish cattle) respond to oral zinc supplements, this condition in bull terriers may be due to an error in zinc metabolism at the cellular level. Attempts to treat one of the pups parenterally with zinc resulted in death after the fourth injection. Résumé— 3 choits d'une portée de 6 Bull Terriers ont développéà l'âge de 7 semaines une dermite podale et faciale exfoliative, crouteuse et alopécique. Les biopsies cutanées pratiquées sur 2 chiots ont révélé une hyperkératose parakératosique compatible avec une carence en zinc, mais les animaux n'ont pas répondu à une supplémentation en zinc. La race, l'anamnèse et l'aspect histologique, sont compatibles avec une acrondermatite léthale du Bull Terrier, maladie familiale, transmise sur un mode autosomal récessif. Des acrodermatites similaires chez l'homme (acrodermatitis enteropatica) et les bovins (anomalie léthale A46 de la Pie Noire Danoise) répondant à une supplémentation en zinc, cette affection chez le Bull Terrier pourrait êtro à une erreur dans le métabolisme du zinc au niveau cellulaire. Un essai de traitement d'un des chiots par vole parcutérale avec du zinc a abouti à sa mort après la quatrième injection. Zusammenfassung— Drei von sechs Bullterrierwelpen aus einem Wurf entwickelten im Alter von 7 Wochen exfoliative, krustige und haarlose Bezirke, besonders an Pfoten und Kopf. Biopsien von zwei der betroffenen Welpen zeigten eine Parakeratose, die bei Zinkmangel auftritt. Die Tiere sprachen jedoch nicht auf orale Zinksubstitution an. Rasse, Anamnese und Befunde der Hautuntersuchung stimmen mit der letalen Akrodermatitis der Bullterrier überein, einem familiären, autosomal rezessiv erblichen Leiden. Während ähnliche akrodermatitische Erkrankungen beim Menschen (Akrodermatitis enteropathica) und beim Rind (Letalfaktor A46 beim schwarzgefleckten Dänischen Rind) auf orale Zinkgaben ansprechen, ist diese Krankheit beim Bullterrier wahrscheinlich auf eine Störung im Zinkmetabolismus auf zellulärer Ebene zurückzuführen. Der Versuch, einen der Welpen parenteral mit Zink zu behandeln, führte zum Tod des Tieres nach der vierten Injektion. Resumen Tres cachorros de Bull Terrier de una camada de seis desarrollaron areas de alopecia exfoliativa, particularmente afectando a los pies y la cabeza, para el momento en que tenian siete semanas de edad. Biopsias de dos de los cachorros afectados revelaron hiperqueratosis paraqueratótica con deficiencia de zinc, pero los perros no respondían a los suplementos de zinc oral. La raza, historia y dermatopatología se consideraron consistentes en acrodermatitis letal de Bull Terriers, una condición que parece ser familial y autosómica recesiva. Mientras que condiciones de acrodermatitis similares en humanos (acrodermatitis enteropética) y ganado (rasgo letal A46 del ganado Black Pied Danish) respondían a los suplementos de zinc oral, esta condición en los Bull Terriers puede ser debida a un error en el metabolismo del zinc a nivel celular. Intentos de trater uno de los cachorros, por vía parenteral con zinc resultaron con la muerte después de la cuarta inyección.     

Hereditary polycystic kidney disease associated with osteorenal syndrome in rats

Hereditary polycystic kidney disease (PKD) was seen in Han:SPRD rats and identified as an autosomal, incomplete dominant trait. Homozygous animals died at 3 to 4 weeks of age, while heterozygous males were severely ill or moribund within about 6 months. Heterozygous females developed PKD to a lesser extent than males and survived longer. Renal secondary hyperparathyroidism and osteodystrophia fibrosa were seen in most males but were absent in females. In male rats metastatic calcification was found in kidneys, lungs, glandular and forestomach, blood vessels, and heart. In a few uremic males ulcerative enteritis occurred in cecum and colon. Blood urea nitrogen values were significantly increased in both sexes.     

Renal anemia in polycystic kidney disease mouse.

DBA/2FG-pcy mice developed the chronic renal failure by the progressive polycystic formation at five months old. Their bilaterally enlarged kidneys occupied about 15% of the body weight. It was about 9 times larger than the normal kidney of DBA/2N mice. A large number of various-sized cysts appeared in cortex and medulla of bilateral light-yellow kidneys of sponge-like shape. Blood urea nitrogen and creatinine increased. Red blood cells (746 +/- 39 x 10(4)/mm3), hemoglobin (8.8 +/- 0.4 g/dl) and hematocrits (31.1 +/- 1.5%) were lower than those of normal control mice. Serum erythropoietin level and reticulocytes did not increase. In addition, the treatment with exogenous erythropoietin improved the anemia in DBA/2FG-pcy mice. It was suggested that the anemia in DBA/2FG-pcy mice was due to the disorder of erythropoietin production caused by the progressive polycystic formation in kidneys.     

Chronic renal failure in an English bull terrier with polycystic kidney disease

An entire female English bull terrier, aged five years and one month, was diagnosed with polycystic kidney disease by renal ultrasonography. It had thickening and abnormal motion of the mitral valve on 2D and M mode echocardiography, and left ventricular outflow tract obstruction, characterised by turbulence in the left ventricular outflow tract and elevated aortic blood flow velocity, detected by colour flow and spectral Doppler echocardiography, respectively. Two years later, haematology, serum biochemistry and urinalysis data suggested the presence of compensated renal failure. The dog was euthanased at 10 years and eight months of age, with haematology, serum biochemistry and urinalysis data Indicating decompensated chronic renal failure. Postmortem examination confirmed polycystic kidney disease, chronic renal disease, mitral and aortic valvular myxomatous degeneration, and mixed mammary neoplasia. This case demonstrates that bull terriers with polycystic kidney disease may develop associated chronic renal failure.     

Familial renal disease in Soft-coated Wheaten Terriers

In two litters of Soft-coated Wheaten Terriers, having the same parents, chronic renal failure developed in five out of ten dogs. The dogs died, or were destroyed on humane grounds, at 7 to 30 months of age. Clinical signs were inappetence, weight loss, vomiting, depression and, in two cases, polydipsia and polyuria. The laboratory data revealed isosthenuria, non-regenerative anaemia, extremely high serum urea nitrogen, and creatinine values. Pathoanatomical findings included small kidneys with an irregular and pale external surface. Cortical lesions were mostly segmental in distribution, and consisted of loss of glomerular elements and increased interstitial connective tissue. Medullary lesions were severe, diffuse in distribution, and consisted of loss of tubules and proliferation of connective tissue. The clinical, laboratory, and pathoanatomical findings show similarities to renal diseases seen in young dogs of other breeds.     

Increased mean arterial pressure and aldosterone-to-renin ratio in Persian cats with polycystic kidney disease

Polycystic kidney disease (PKD) in Persian cats has been increasingly reported and compared to human autosomal dominant polycystic kidney disease (ADPKD) in the last decade. In cats, however, few studies have dealt with the occurrence and hormonal determinants of hypertension, one of the most common extrarenal manifestations of ADPKD in humans. The purpose of this study was to compare Persian cats >4 years old with PKD to unaffected control cats with regard to blood pressure (BP), plasma renin activity (PRA), serum aldosterone concentration, plasma atrial natriuretic peptide (ANP) concentration, and aldosterone-to-renin ratio (ARR). Three gender- and age-matched groups were studied, each consisting of 7 cats: (1) a control group without cysts, (2) a group with mild PKD, and (3) a group with severe PKD (multiple cysts and renal enlargement). Mild renal insufficiency was found in only 1 of 14 cats with PKD. Cats with PKD had a higher mean arterial pressure (P = .04) and more often had a high ARR (P = .047) than did control cats. Tendencies toward higher diastolic and systolic arterial pressures (DAPs and SAPs, respectively) and lower PRAs were observed in cats with PKD compared to controls (.05 < P < or = .1). No significant differences were found between the groups in serum aldosterone and plasma ANP concentrations. None of the cats had echocardiographic evidence of cardiac hypertrophy. In conclusion, cats with PKD had a minor increase in mean arterial pressure compared to control cats, and half of the cats had a high ARR.     

Blood, Bull Terriers and Babesiosis: further evidence for direct transmission of Babesia gibsoni in dogs

This study reports on the epidemiology of Babesia gibsoni in American Pit Bull Terriers living in a region of western Victoria in southern Australia. Both American Pit Bull Terriers (n = 100) and other dog breeds (n = 51) were screened for B gibsoni using immunofluorescent antibody testing (IFAT) and/or polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). A questionnaire was also completed by each dog owner, ascertaining the husbandry and habits of the dogs sampled. Fourteen dogs were positive for B gibsoni using IFAT and/or PCR-RFLP and all were American Pit Bull Terriers. Dogs that were male and/or had been bitten by or were biters of other American Pit Bull Terriers were more likely to be B gibsoni positive, thus suggesting that blood-to-blood transmission contributes to the spread of this disease between dogs.     

von Willebrand's disease in Scottish Terriers in Australia

SUMMARY Over a 5-year period (1988–92), von Willebrand factor antigen (vWf:Ag) assays were performed on plasma samples from 207 Scottish Terriers. Based on these tests, 47 dogs (23%) had vWf:Ag concentrations < 50 canine units (CU)/dL and were classified as heterozygous carriers of the von Willebrand's disease (vWD) gene, while 9 (4%) had concentrations below the sensitivity of the assays and were classified as homozygous. There was thus an overall prevalence of 27% for the vWD gene in the Scottish Terriers tested. The homozygous dogs (median age 0.6 years at diagnosis) consisted of 7 males and 2 females. Eight of these had haemorrhage attributable to the disease, mostly spontaneous and from the oral mucosa. Other signs included haemorrhage induced by trauma or surgery, easy bruising and epistaxis. Many haemorrhagic episodes were severe enough to warrant therapeutic intervention and there was a single fatality. Pedigree analysis, possible in 7 of the dogs, revealed that each was the progeny of a mating between dogs with vWf:Ag concentrations < 50 CU/dL, which supported an autosomal recessive mode of inheritance. A single heterozygous carrier suffered haemorrhage after surgery that, in contrast to the homozygotes, was mild and did not require therapy. The data indicate that vWD is a significant problem in Scottish Terriers in Australia. Accordingly, we recommend that steps be taken to reduce the prevalence of the disease and thereby the number of clinically affected dogs, such as the establishment of a national testing scheme to determine the vWD status of all breeding dogs.