Membranous nephropathy in the cat: a clinical and pathological study

A series of 13 cases of feline membranous nephropathy is presented. Two groups were distinguished clinically; eight cats had the nephrotic syndrome and five others were in renal failure but not nephrotic. The definitive diagnosis was based on histological, immunofluorescence and ultrastructural examinations of renal tissue obtained at renal biopsy or necropsy. Glomerular lesions were classified according to the degree of glomerular change into three distinct groups; mild, moderately severe and advanced. A relationship was established between the mild and moderately severe groups and cats with the nephrotic syndrome, and the advanced group and cats in renal failure. Diuretic therapy was satisfactory in initial control of oedema in the nephrotic cases. Monitoring of previously nephrotic cats for up to three years indicated that the disease is progressive, although in some cases it is sufficiently slow for a cat to live a relatively normal life without continuing treatment. The prognosis for cats presented in renal failure is hopeless.     

Progressive retinal atrophy in Abyssinian and Somali cats in the Netherlands (1981-2001)

From 1981 to 2001, 248 Abyssinian and 127 Somali cats in the Netherlands were examined for hereditary eye disease. Distinct ophthalmoscopic signs consistent with hereditary progressive retinal atrophy (PRA) were observed in 11 Abyssinian cats, and subtle signs in 3 Abyssinian cats. A familial relationship was detected in 13 out of 14 of these cats, which supports a hereditary basis to the condition. Distinct funduscopic signs of retinal degeneration were observed at a median age of 4 years. One cat with advanced retinal degeneration was only 7 months old, whereas the remaining 10 cats were between 2 and 12 years old at the time of diagnosis. These differences in the age of onset are suggestive of at least two types of PRA occurring in Abyssinian cats in the Netherlands: a dysplastic, early-onset and a late-onset retinal degeneration. A large-scale and systematic examination programme for hereditary eye disease will be necessary to assess the incidence of PRA in the Dutch population of Abyssinian and Somali cats as a whole, and to provide a basis for a preventive breeding programme.     

Experimental immune complex glomerulonephritis and the nephrotic syndrome in cats immunised with cationised bovine serum albumin

Membranous nephropathy was induced in four cats by repeated intravenous injections of 120 mg cationic bovine serum albumin (BSA, pI 9.5). All four cats developed diffuse granular deposits of IgG and C3 along the glomerular capillary walls as early as five weeks which persisted until the end of the experiment at 17 weeks. Ultrastructural studies revealed many subepithelial electron dense deposits. Two cats developed severe proteinuria and the nephrotic syndrome characterised by hypoalbuminaemia and oedema. An additional four cats received repeated injections of unmodified native BSA (pI 4.5) and remained basically normal. This is the first report of membranous nephropathy and the nephrotic syndrome in an experimental animal model which, unlike other animal models, is subject to the spontaneously occurring disease.     

Natural remission of nephrotic syndrome in a dog with immune-complex glomerular disease.

A nephrotic syndrome caused by immune-complex glomerular disease was diagnosed in a 4-year-old male Great Dane. The syndrome was characterized by proteinuria, hypoproteinemia, hypoalbuminemia, hypercholesterolemia, and subcutaneous edema. Renal biopsy revealed segmental membranous glomerular disease. The edema underwent complete remission 18 days after admission. Two months after admission, there was no clinical or laboratory evidence of glomerular disease. Periodic reevaluation of the dog during the next 2 years revealed recurrence of proteinuria, but no other clinical or laboratory abnormalities. Serial renal biopsies revealed persistence, but no appreciable increase, in the severity of the segmental membranous glomerular disease. The natural course of the nephrotic syndrome and immune-complex glomerular disease has been associated with unpredictable variability. It was concluded that the widespread use of corticosteroid or immunosuppressant therapy in dogs with immune complex glomerular disease should be withheld until the natural course of the disease has been evaluated in a significant number of patients and until the results of well-controlled clinical studies confirm or deny their therapeutic value.     

Familial renal amyloidosis in Abyssinian cats

Medullary and glomerular amyloidosis, papillary necrosis, and secondary interstitial disease were diagnosed in eight related adult Abyssinian cats from two catteries. The lesions were similar to those in two unrelated mongrel cats with renal amyloidosis. Ultrastructurally, the patterns of amyloid deposition were as described in other species, although medullary deposition predominated. Potassium permanganate oxidation blocked Congo red staining of the deposits suggesting that they contained amyloid A protein (secondary amyloid). The disease may be a model of familial secondary amyloidosis and offers an opportunity to study the pathogenesis of both amyloid deposition and papillary necrosis. The histochemical characteristics of feline renal amyloid require careful attention to technique. Section thickness affects Congo red affinity and both dichroism as well as birefringence should be considered when interpreting staining reactions. Thioflavine-T may be the preferred stain for identification of small deposits of amyloid. Variation in section thickness markedly affected the degree of potassium permanganate oxidation.     

Naturally occurring canine nephrotic syndrome is a potentially hypercoagulable state

Fourteen dogs with naturally occurring nephrotic syndrome were evaluated for abnormalities in the hemostatic system. Histopathologic diagnoses included 8 dogs with membraneous glomerulonephritis, 1 dog with acute glomerulon-ephritis, 2 dogs with idiopathic glomerulopathy, and 2 dogs with amyloidosis. The coagulation protein assays performed included concentrations of factors V, VII, VIII: C, IX, X, fibrinogen (I), anti-thrombin III, and plasminogen. Thrombocyte counts were also performed. All of these analytes were significantly elevated (P < 0.05) with the exception of ATIΠ which was significantly decreased (P < 0.05). Five of the dogs had histologic evidence and 1 dog had angiographic evidence of thrombosis and thromboembolism. Naturally occurring canine nephrotic syndrome thus represents a potentially hypercoagulable state and may serve as a valuable model in the study of certain components of the human disease.     

Serum amyloid A protein concentration measured by radial immunodiffusion in Abyssinian and non-Abyssinian cats

Serum amyloid A (SAA) protein concentration was determined by use of radial immunodiffusion (RID) in 4 groups of cats: Abyssinian cats with amyloidosis, healthy Abyssinian cats without clinical evidence of amyloidosis, hospitalized non-Abyssinian cats, and clinically normal non-Abyssinian cats. Mean SAA concentration in Abyssinian cats with amyloidosis was significantly (P = 0.05) higher than mean SAA concentration in healthy Abyssinian cats without clinical evidence of amyloidosis and in hospitalized non-Abyssinian cats. Mean SAA concentration in clinically normal non-Abyssinian cats was significantly (P = 0.05) lower than mean SAA concentration in healthy Abyssinian cats without clinical evidence of amyloidosis and in hospitalized non-Abyssinian cats. Affected and healthy Abyssinian cats, however, could not reliably be distinguished on the basis of SAA concentration, because of the wide range of SAA values in these 2 groups of cats.     

Pedigree analysis of Abyssinian cats with familial amyloidosis

Pedigrees of 62 Abyssinian cats with familial amyloidosis were compared with those of 100 Abyssinian cats registered with the Cat Fanciers Association. The inbreeding coefficients of the 2 samples of cats were not significantly different. Analysis of the pedigrees with respect to specific ancestors, however, showed that certain cats were significantly more common in the pedigrees of affected cats than in those of cats in the randomly selected sample. These data support a genetic basis for this disease, but do not allow determination of the mode of inheritance.     

Noncongophilic fibrillary glomerulonephritis in a cat

This report describes an uncommon case of nonamyloidotic fibrillary glomerulonephritis. A 5-year-old female European cat was presented with nephrotic syndrome. Serum biochemistry and urinalysis revealed a mild increase in cholesterol, low total protein, severe hypoalbuminemia, and high proteinuria with a high protein-to-creatinine ratio. An histologic examination revealed an interstitial nephritis and a diffuse glomerulonephritis, with multifocal thickening of the Bowman's capsule. Transmission electron microscopy showed widespread fibrillary deposits in the glomerular basement membrane and in the mesangium. These fibrils ranged between 18 and 26 nm in diameter and were Congo red negative, which allowed their differentiation from amyloid. Immunohistochemistry demonstrated expression for immunoglobulin M (IgM) and immunoglobulin G (IgG) within the mesangium. Renal deposits of Congo red-negative amyloid-like fibrils have been described in humans, horses, monkeys, and dogs. This is the first report of noncongophilic fibrillary glomerulopathy in a cat.     

Anemia, splenomegaly, and increased osmotic fragility of erythrocytes in Abyssinian and Somali cats

OBJECTIVE: To determine clinical and clinicopathologic features of a chronic intermittent severe hemolytic anemia characterized by erythrocyte osmotic fragility in Abyssinian and Somali cats. DESIGN: Case series. ANIMALS: 13 Abyssinian and 5 Somali cats. PROCEDURES: History, pedigree information, and results of routine laboratory tests, special erythrocyte studies, and histologic evaluation of splenic and hepatic specimens were analyzed. RESULTS: Age at which clinical signs of anemia were first apparent ranged from 6 months to 5 years. Ten cats had splenomegaly. Most often, the PCV was between 15 and 25%, but it was as low as 5% at some times. The anemia was characterized by macrocytosis and mild to moderate reticulocytosis, but no poikilocytosis. Hyperglobulinemia, lymphocytosis, mild hyperbilirubinemia, and high hepatic enzyme activities were common findings. Results of Coombs tests and tests for infectious diseases were negative. The erythrocytic osmotic fragility was high in affected cats (mean osmotic fragility, 0.66 to 0.78%), compared with healthy cats (0.48 to 0.58). No specific membrane protein abnormality, erythrocyte enzyme deficiency, or hemoglobinopathy was identified. Histologic evaluation of splenic and hepatic specimens revealed extramedullary hematopoiesis and hemosiderosis. Four of the 5 Somali cats were closely related. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of results of pedigree analyses, the apparent breed predilection, and the exclusion of other known causes of anemia in cats, we believe that the hemolytic anemia in these cats was likely a result of a novel hereditary erythrocyte defect. A genetic predisposition to immune-mediated destruction of erythrocytes could not be ruled out.     

Real-time PCR genotyping assay for feline erythrocyte pyruvate kinase deficiency and mutant allele frequency in purebred cats in Japan

Erythrocyte pyruvate kinase (PK) deficiency is an inherited glycolytic erythroenzymopathy caused by mutations of the PKLR gene. A causative mutation of the feline PKLR gene was originally identified in Abyssinian and Somali cats in the U.S.A. In the present study, a TaqMan probe-based real-time PCR genotyping assay was developed and evaluated for rapid genotyping and large-scale screening for this mutation. Furthermore, a genotyping survey was carried out in a population of four popular purebred cats in Japan to determine the current mutant allele frequency. The assay clearly displayed all genotypes of feline PK deficiency, indicating its suitability for large-scale survey as well as diagnosis. The survey demonstrated that the mutant allele frequency in Abyssinian and Somali cats was high enough to warrant measures to control and prevent the disease. The mutant allele frequency was relatively low in Bengal and American Shorthair cats; however, the testing should still be carried out to prevent the spread of the disease. In addition, PK deficiency should always be considered in the differential diagnosis of anemia in purebred cats in Japan as well as worldwide.     

Progressive retinal atrophy in the Abyssinian cat

Eight cases of hereditary progressive retinal atrophy in Abyssinian cats in Denmark are reported. Pedigree studies indicate direct lineage to affected cats of the same breed in Sweden. The disease is bilateral, progressive, and of the generalized type, and ultimately leads to blindness.     

Immunohistochemical studies of cone photoreceptors and cells of the inner retina in feline rod-cone degeneration

Previous studies using electroretinography and immunohistochemistry have shown normal cone function and structure in early stages of hereditary rod‐cone degeneration of Abyssinian cats. To further investigate the cone photoreceptors and the inner retina of dystrophic cats, antibodies against green‐ and blue‐sensitive cones and specific cell types of inner retina were used in seven cats with the recessively inherited rod‐cone degeneration, and three normal European short‐haired cats. There was a reduction in number of both types of cones early in the disease. Changes at early stages of disease also occurred among horizontal cells in which there was an extension and a thickening of their lateral processes. The regular configuration of bipolar cells was changed in the more advanced stages of disease and their apical dendrites were lost. Abnormalities were not observed in the amacrine cells and in the ganglion cell layer in any of the present cases. This study shows that the cone system is morphologically abnormal in young cats at an earlier stage of disease than previously shown. The present findings also support the assumption that the inner retina is largely preserved throughout the disease process.     

Pulmonary Thromboembolism in Dogs

Pulmonary thromboembolism (PTE) is an infrequently diagnosed complication of many systemic diseases including heartworm disease, glomerulopathy leading to the nephrotic syndrome, immune-mediated hemolytic anemia, hyperadrenocorticism, pancreatitis, neoplasia, and sepsis. Acute, unexplained dyspnea in a patient with minimal abnormalities on thoracic radiographs should prompt consideration of this diagnosis. Confirmation requires ventilation-perfusion radionuclide scanning or selective pulmonary angiography. Treatment includes cage rest, anticoagulant therapy with heparin and warfarin, correction of the underlying disorder, and supportive care. Clinicians should be prepared to treat hemorrhage associated with anticoagulant therapy. Recombinant tissue plasminogen activator may prove useful as a thrombolytic in the treatment of animals suffering massive PTE, but is, at present, expensive.     

Six cases of progressive retinal atrophy in Abyssinian cats

Six cases of a type of progressive retinal atrophy in Abyssinian cats are recorded. This condition appears to be late in onset (approximately six years of age) and progresses relatively slowly after its initial appearance in the central retina. Only cats which reach an advanced age appear to become completely blind as a result of disease progression. Histopathological findings from one case are described and the condition is discussed and contrasted with previously published cases of progressive retinal atrophy in the breed.     

The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease

Feline inflammatory bowel disease (IBD) is the term applied to a group of poorly understood enteropathies that are considered a consequence of uncontrolled intestinal inflammation in response to a combination of elusive environmental, enteric microbial, and immunoregulatory factors in genetically susceptible cats. The present study sought to examine the relationship of mucosal bacteria to intestinal inflammation and clinical disease activity in cats with inflammatory bowel disease. Duodenal biopsies were collected from 27 cats: 17 undergoing diagnostic investigation of signs of gastrointestinal disease, and 10 healthy controls. Subjective duodenal histopathology ranged from normal (10), through mild (6), moderate (8), and severe (3) IBD. The number and spatial distribution of mucosal bacteria was determined by fluorescence in situ hybridization with probes to 16S rDNA. Mucosal inflammation was evaluated by objective histopathology and cytokine profiles of duodenal biopsies. The number of mucosa-associated Enterobacteriaceae was higher in cats with signs of gastrointestinal disease than healthy cats (P<0.001). Total numbers of mucosal bacteria were strongly associated with changes in mucosal architecture (P<0.001) and the density of cellular infiltrates, particularly macrophages (P<0.002) and CD3(+)lymphocytes (P<0.05). The number of Enterobacteriaceae, E. coli, and Clostridium spp. correlated with abnormalities in mucosal architecture (principally atrophy and fusion), upregulation of cytokine mRNA (particularly IL-1, -8 and -12), and the number of clinical signs exhibited by the affected cats. These data establish that the density and composition of the mucosal flora is related to the presence and severity of intestinal inflammation in cats and suggest that mucosal bacteria are involved in the etiopathogenesis of feline IBD.     

Risk factors for feline infectious peritonitis in Australian cats

The objective of this study was to determine whether patient signalment (age, breed, sex and neuter status) is associated with naturally-occurring feline infectious peritonitis (FIP) in cats in Australia. A retrospective comparison of the signalment between cats with confirmed FIP and the general cat population was designed. The patient signalment of 382 FIP confirmed cases were compared with the Companion Animal Register of NSW and the general cat population of Sydney. Younger cats were significantly over-represented among FIP cases. Domestic crossbred, Persian and Himalayan cats were significantly under-represented in the FIP cohort, while several breeds were over-represented, including British Shorthair, Devon Rex and Abyssinian. A significantly higher proportion of male cats had FIP compared with female cats. This study provides further evidence that FIP is a disease primarily of young cats and that significant breed and sex predilections exist in Australia. This opens further avenues to investigate the role of genetic factors in FIP.     

Treatment of three cats with hyperviscosity syndrome and congestive heart failure using plasmapheresis

Three cats were evaluated at a veterinary teaching hospital for congestive heart failure (CHF) secondary to hyperviscosity syndrome from plasma cell neoplasia. All cats had severe hyperproteinemia due to hyperglobulinemia. Multiple myeloma or plasma cell neoplasia was diagnosed based on cytopathology and post mortem examination. The cats presented with signs of CHF including acute collapse, tachypnea, increased respiratory effort, and pulmonary crackles. All cats had heart murmurs and echocardiographic signs consistent with hypertrophic cardiomyopathy. An enlarged left atrium was found in all cats and two of three cats also had spontaneous echocardiographic contrast. Plasmapheresis (centrifugal plasma exchange) was performed on all three cats by the removal of whole blood and the infusion of a balanced electrolyte solution while the whole blood was centrifuged and separated. The RBCs were then washed before being readministered to the patient. Plasmapheresis alleviated the clinical signs of CHF (tachypnea) in all three cats. Plasmapheresis should be considered in cases of CHF secondary to hyperviscosity syndrome to rapidly alleviate clinical signs associated with heart failure while diagnosis of the underlying cause is made and appropriate therapy implemented.