Glomerulonephritis In Dogs Research Articles

The pathogenetic role of glycoproteins and proteoglycans in dog glomerulonephritis

The aim: to determine the main pathogenetic links of glomerulonephritis in dogs with the participation of connective tissue biopolymers.
 Materials and methods The research was conducted by analyzing the sources of scientific literature (PubMed, Elsevier, electronic resources of the V. I. Vernadskyi National Library) and the clinical experience of the authors, thanks to which a scheme of the pathogenesis of glomerulonephritis in dogs with the participation of connective tissue biopolymers was developed.
 Results. According to the results of our research, it was established, that chronic glomerulonephritis in dogs is accompanied by neutrophilia, lymphocytosis, as well as urinary and nephrotic syndromes, the progression of which causes a violation of the functional state of the kidneys and liver. Sick dogs develop a nephrotic symptom complex – persistent proteinuria, hypoalbuminemia, dysproteinemia, and hyperlipidemia. Clinically, edema was not observed, because it is known, that in dogs they are rarely detected with nephrotic syndrome. Inflammation in the kidneys is accompanied by an increase in the concentration of glycoproteins and sialic acids in the blood serum. After treatment, there was a decrease in the inflammatory process in the kidneys, which was manifested by a decrease in neutrophilia and lymphocytosis, as well as the content of glycoproteins and sialic acids in the blood serum. The content of total chondroitin sulfates and the fractional composition of glycosaminoglycans did not change, and the level of excretion of oxyproline and uronic acids decreased compared to the indicators before the start of treatment. This, in our opinion, is due to the slowing down of fibrotic processes in the kidneys. Thus, biochemical indicators of the state of connective tissue in the blood serum and urine of dogs with glomerulonephritis allowed us to evaluate the functional state of the kidneys for their inflammation (oxyproline and uronic acids), as well as to determine the violation of proteoglycan synthesis in nephrotic syndrome.
 Conclusions. For glomerulonephritis in dogs on the background of depression, decreased appetite, polydipsia, pain during palpation in the lumbar region, periodic vomiting, neutrophilic leukocytosis, lymphocytosis, nephrotic syndrome (hypoalbuminemia, increase in α2- and β-globulins, cholesterol, β-lipoproteins), growth activity of ALT, AST, and alkaline phosphatase, a decrease in Veltman's test, hyperazotemia, hyperphosphatemia, proteinuria, microhematuria, and cylindruria, there is an increase in the content of glycoproteins, sialic acids, and chondroitin sulfates, as well as heparan sulfate in the blood serum of dogs. The increase in the blood serum of patients with canine glomerulonephritis, as a marker of connective tissue – glycoproteins, sialic acids, chondroitinsulfates, and urinary excretion of oxyproline and uronic acids is due to inflammatory and fibrotic changes in the basal membranes of the kidney glomeruli

Occurrence, management and outcome of immune-complex glomerulonephritis in dogs with suspected glomerulopathy in the UK.

To determine the proportion of dogs diagnosed with immune-complex glomerulonephritis in a large cohort of UK dogs with clinical suspicion of glomerular disease in which renal histopathology, including routine light microscopy, transmission electron microscopy and immunofluorescence, had been performed. The second objective was to describe treatment and long-term clinical outcome of dogs diagnosed with immune-complex glomerulonephritis. Sixty-two UK dogs that underwent renal biopsies for investigation of suspected glomerulopathy (urine protein-to-creatinine ratio persistently >0.5) were included in this retrospective multicentre study. Signalment, clinico-pathological abnormalities, histopathological diagnosis, treatment following diagnosis and survival were recorded. Seventeen (27%) of the dogs with suspected glomerular disease were diagnosed with immune-complex glomerulonephritis and nine (53%) of these were still alive at the study end point, with a median follow-up of 366 days (range 52 to 1299). Six dogs diagnosed with immune-complex glomerulonephritis were treated with mycophenolate. Four received mycophenolate alone for immunosuppression and two received mycophenolate and chlorambucil; all these six dogs were alive at data collection [median follow-up time 712.5 days (range 73 to 1299)]. Seven dogs diagnosed with immune-complex glomerulonephritis did not receive immunosuppressive treatment; only one of these dogs was alive at study end point [median survival time 302 days (range 52 to 723)]. Immune-complex glomerulonephritis may be less common in the UK than previously reported in North America and mainland Europe, reducing the likelihood of treatment modification following renal biopsy. Mycophenolate was the most commonly used immunosuppressant for cases of immune-complex glomerulonephritis.

Paraffin immunofluorescence for detection of immune complexes in renal biopsies: an efficient salvage technique for diagnosis of glomerulonephritis in dogs

BackgroundRenal biopsy is an essential tool for the diagnosis of proteinuric kidney diseases in dogs, and evaluation of immune complexes (IC) by immunofluorescence (IF) of frozen sections (IF-F) is required for the diagnosis of IC-mediated glomerulonephritis (ICGN). However, the use of frozen sections from renal biopsies can have limitations. The aim of this study was to develop a reliable IF method using formalin-fixed and paraffin-embedded (FFPE) sections to detect ICs in dog ICGN.MethodsRenal biopsy specimens were obtained from dogs with protein-losing nephropathies. FFPE sections were prepared, and eight antigen retrieval pretreatment protocols were performed: digestion with trypsin, microwave (MW) heating in citrate buffer (MW-CB; pH 6.0), MW heating in Tris-EDTA buffer (MW-TEB; pH 9.0), as well as combinations of the above, and a non-treated control.ResultsA combination of trypsin for 30 min (Try-30) and MW-TEB; pH 9.0 was the most effective antigen retrieval pretreatment, with clear positive signals for IgG, IgA, IgM, and C3 detected by IF-FFPE. Granular signals, an important diagnostic indicator of ICGN, were clearly observed by both IF-F and IF-FFPE after combined pretreatment with Try-30 and MW-TEB, and IgG, IgA, IgM, and C3 signals were almost completely matched in all samples by IF-F and IF-FFPE.ConclusionIF-FFPE with Try-30 and MW-TEB pretreatment is a valuable technique for the diagnosis of renal diseases in dogs. This method could be an efficient tool when standard IF-F cannot be used, or does not provide useful results due to lack of glomeruli in the specimens for IF-F.

Renal histomorphology in dogs with pyometra and control dogs, and long term clinical outcome with respect to signs of kidney disease

BackgroundAge-related changes in renal histomorphology are described, while the presence of glomerulonephritis in dogs with pyometra is controversial in current literature.MethodsDogs with pyometra were examined retrospectively for evidence of secondary renal damage and persisting renal disease through two retrospective studies. In Study 1, light microscopic lesions of renal tissue were graded and compared in nineteen dogs with pyometra and thirteen age-matched control bitches. In Study 2, forty-one owners of dogs with pyometra were interviewed approximately 8 years after surgery for evidence ofclinical signs of renal failure in order to document causes of death/euthanasia.ResultsInterstitial inflammation and tubular atrophy were more pronounced in dogs with pyometra than in the control animals. Glomerular lesions classified as glomerular sclerosis were present in both groups. No unequivocal light microscopic features of glomerulonephritis were observed in bitches in any of the groups.Two bitches severely proteinuric at the time of surgery had developed end stage renal disease within 3 years. In five of the bitches polyuria persisted after surgery. Most bitches did not show signs of kidney disease at the time of death/euthanasia.ConclusionTubulointerstitial inflammation was observed, but glomerular damage beyond age-related changes could not be demonstrated by light microscopy in the dogs with pyometra. However, severe proteinuria after surgery may predispose to development of renal failure.

Increased prevalence of Borrelia burgdorferi infections in Bernese Mountain Dogs: a possible breed predisposition

BackgroundGlomerulonephritis in dogs has been associated with B. burgdorferi infections. In Bernese Mountain Dogs with glomerulonephritis antibodies against B. burgdorferi have been found in most dogs, raising the question if the breed is predisposed to infections with B. burgdorferi. The aim of this study was to determine the prevalence of antibodies against B. burgdorferi sensu lato in a well defined population of Bernese Mountain Dogs and to compare this prevalence with data from dogs of other breeds.Results160 Bernese Mountain Dogs and 62 control dogs (large breed dogs with long hair) were included. All dogs were considered healthy according to a questionnaire filled out by the owner, complete blood count, chemistry panel, urinalysis and urine culture. Bernese Mountain Dogs and control dogs were kept in similar environments. Seroprevalence of B. burgdorferi was assessed by ELISA and Western blot and was 58% in Bernese Mountain Dogs compared to 15% in control dogs. This difference was significant. Neither antibodies against leptospires nor vaccination or hair coat color influenced the results.ConclusionThe cause of the considerably higher prevalence of antibodies against B. burgdorferi in Bernese Mountain Dogs and it's consequences are not known. A breed predisposition can be suspected.

Dirofilaria immitis: Detection of parasite-specific antigen by monoclonal antibodies in glomerulonephritis in infected dogs

For the identification of circulating parasite antigens associated with immune-complex glomerulonephritis in dogs infected with Dirofilaria immitis, monoclonal antibodies (mAbs) were generated against adult worms. A total of 11 mAbs were selected for cloning because of their high productivity and their lack of cross-reactivity with Toxocara canis in indirect immunofluorescence tests. The ability of mAbs to detect circulating antigens was examined using an antigen-capture enzyme-linked immunosorbent assay. Of the 11 mAbs, only NAK-1, an IgG2a mAb, was capable of detecting circulating antigens in 75% of infected dogs. However, this mAb was highly species-specific in its detection of circulating antigens, since sera from dogs infected with other nematode parasites were negative. Furthermore, the mAb detected antigens at the same glomerular sites in which IgG and/or C3 were deposited. The antigen deposits were observed along capillaries and/or in mesangial cells. The epitope recognized by this mAb is probably a carbohydrate, as it remained stable for 1 h at 100 degrees C and was sensitive to periodate treatment. Two bands of 62 and 26 kDa, respectively, were detected on Western blots by the mAb when sera from dogs infected with D. immitis were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transblotted.

Effects of a thromboxane synthetase inhibitor on established immune complex glomerulonephritis in dogs

Summary Twelve Beagles were inoculated with concanavalin A, and after a mean ninefold increase in antibody titer, 1 mg of concanavalin A was infused into each renal artery of each dog to induce in situ immune complex glomerulonephritis. Starting 4 weeks after renal arterial infusion, 6 dogs were treated orally 3 times daily with 30 mg of 3-methyl-2 (3 pyridyl)-1-indoleoctanoic acid (CGS 12970)/ kg of body weight, a thromboxane synthetase inhibitor, and 6 dogs (control group) received a gelatin capsule 3 times daily. Endogenous creatinine clearance and 24-hour urinary excretion of protein and thromboxane B2 were determined for each dog prior to renal arterial infusion, at the initiation of treatment and at 2, 4, 6, and 8 weeks after initiation of treatment. In addition, methyoxy-3H inulin clearance was determined at initiation of treatment and 4 and 8 weeks later. Renal specimens were examined histologically at the initiation of treatment and 4 and 8 weeks later. Glomerular mononuclear profiles/μm3 were determined from at least 10 equatorially sectioned glomeruli from each dog. Paired t tests were used to compare mean values at the various time points to the respective mean baseline value and 2-sample t tests were used to evaluate differences between treatment groups. At the start of treatment (4 weeks after renal arterial infusion of concanavalin A), histologic evaluation of renal specimens revealed glomerular epithelial crescent formation, mononuclear cell proliferation, and infiltration of neutrophils. Mononuclear cell profiles and urinary excretion of protein and thromboxane B2 were significantly increased, but endogenous creatinine clearance values were unchanged. Treatment with CGS 12970 did not affect endogenous creatinine clearance, methyoxy-3H inulin clearance, or glomeruli, however, CGS 12970 treatment significantly decreased urinary excretion of protein and thromboxane B2 when compared with values in the control group. These findings suggested that thromboxane has a role in the pathogenesis of established glomerulonephritis and that thromboxane synthetase inhibition treatment may be beneficial in dogs with established glomerulonephritis.

Membranoproliferative glomerulonephritis in dogs with a genetically determined deficiency of the third component of complement

Renal disease is a common clinical manifestation of genetically determined deficiencies of the complement system in man. Like their human counterparts, dogs with a genetically determined complete deficiency of C3 also develop renal disease. Five of 20 C3-deficient dogs developed clinical evidence of renal failure. However, 14 of the 15 remaining dogs had histological evidence of type I membranoproliferative glomerulonephritis. The lesions were characterized by measangial cell proliferation, an incrase in the mesangial matrix, thickening of the glomerular capillary wall, electron-dense deposits in the mesangium and subendothelial space, and the presence of IgG and IgM. In order to determine the effect of treatment with C3 on the renal disease of C3-deficient dogs, two C3-deficient dogs were infused with normal canine plasma twice weekly for 3 weeks. Their urinary protein excretion rose progressively from less than 200 mg 24 hr to greater than 1000 mg 24 hr ; renal function remained normal. Renal biopsies performed 1 week after the last infusion revealed more severe glomerulonephritis and the presence of C3. As controls, a C3-deficient dog was given C3-deficient canine plasma and a normal dog was given normal canine plasma; neither control animal developed proteinuria or changes in their renal biopsy. These observations suggest that renal disease may be more common in humans with complement deficiencies than would be suspected based on clinical assessment. Furthermore, these results suggest that treatment with complement-containing blood products may worsen preexisting renal disease in complement-deficient individuals.

Experimental immune complex glomerulonephritis in dogs receiving cationised bovine serum albumin

Eight 16-week-old dogs were used to induce immune complex glomerulonephritis by daily intravenous injections of 120 mg highly cationized bovine serum albumin (pI9.5). Of four control dogs, two received unmodified native anionic bovine serum albumin (pI 4.5) while the other two received only phosphate buffered saline. The renal glomeruli were examined by light, electron (transmission and scanning) and immunofluorescence microscopy at intervals from five to 11 weeks after the start of the injections. Animals receiving cationic antigen all developed generalised diffuse granular deposits of IgG and C3 along the capillary walls; these were detected as early as five weeks and continued until the termination of the experiment at 11 weeks. Ultrastructural studies revealed many electron dense deposits along the subepithelial regions of the glomerular basement membrane. The experimental disease resembled in many respects naturally occurring membranous nephropathy, the most common form of immune complex glomerulonephritis in dogs.

Comparative Pathology of Glomerulonephritis in Animals

Glomerulonephritis constitutes an important category of renal diseases in animals and has been recognized with increasing frequency in the last decade. We report here the comparative morphologic aspects of glomerulonephritis as a naturally occurring disease of animals. We briefly review the immunopathogenesis of glomerulonephritis. The morphology of renal lesions occurring in glomerulonephritis in dogs, cats, cattle, sheep, horses and swine has been reviewed with emphasis on the range and specificity of various glomerular lesions and on the comparison of lesions between various species. A distinction was made between glomerulonephritis as a primary disease entity and glomerulonephritis associated with other disease processes. Primary idiopathic glomerulonephritis occurred in all species but was most commonly recognized as a clinically important disease in dogs and cats. Glomerulonephritis also occurred in association with other diseases such as equine infectious anemia, chronic hog cholera, canine pyometra, dirofilariasis, feline leukemia virus infection and canine systemic lupus erythematosus.

GLOMERULONEPHRITIS PRODUCED IN DOGS BY SPECIFIC ANTISERA

The intravenous injection of rabbit antidog-placenta or antidog-kidney serum produced immediate evidence of glomerulonephritis in dogs. The lesions produced by the two agents were indistinguishable. The glomerulonephritis so induced may terminate in death within 8 days, may progress to a chronic form or may heal. The acute phase of the nephritis was usually associated with severe exudative and necrotizing renal lesions, while the pathologic sequences in surviving dogs were essentially reparative. However, 1 dog of 8 in the chronic phase developed a progressive chronic nephritis and died in uremia.

Experimental Bacterial Endocarditis and Proliferative Glomerulonephritis: Description of Method of Production Utilizing Bilateral Lower Extremity or Single Aorta-Vena Cava Arteriovenous Fistulas

SUMMARY AND CONCLUSIONS 1)By combining the effects of systemic cardiovascular stress produced by large arteriovenous fistula loads with bacteremia, a new method has been described for the experimental production of endocarditis and acute diffuse proliferative glomerulonephritis in dogs. 2)Bilateral lower extremity (iliac and femoral), or single aorta-vena cava fistulas are effective for use in this experimental method. 3)Seventeen unoperated normal dogs were given injections of bacterial organisms in numbers up to 14,000 times the numbers of bacteria of the same species and strains as were followed by heart valve or kidney lesions in the dogs with large arteriovenous fistula loads. There was in no instance the occurrence of either endocarditis nor glomerulonephritis in these normal dogs. 4)Likewise, in 10 dogs with single femoral arteriovenous anastomoses receiving intravenous injections of bacteria in comparable numbers, neither endocarditis nor glomerulonephritis occurred. 5)Because of the absence of lesions in the unoperated normal dogs and dogs with single femoral arteriovenous shunts given the same bacteria in the same or much larger numbers than given to the animals with large fistulas subsequently showing valvular or renal lesions, it is concluded that the increased work of the heart plays a major role in determining the susceptibility of these animals to endocarditis and glomerulonephritis. 6)The pathogenesis of these experimental observations depends upon the fact that increasing the work of the heart by means of large arteriovenous fistula loads create or set in motion certain mechanical and, or endocrine alterations which in turn produce a specific and significant increase (up to 14,000 times) in the susceptibility of the endothelial surfaces of the heart and kidneys to bacterial infection. The factual data supporting these conclusions are presented. 7)By utilizing these experimental methods, it may be possible to identify more precisely the physiological alterations which occur in response to increased cardiovascular work and which are apparently responsible for this great increase in susceptibility to bacterial infection observed in these studies. Such accomplishments, might forecast the development of more effective methods of prophylaxis and therapy for endocarditis, glomerulonephritis, and possibly for bacterial infections in general.