Renal lesions in MRL mice

Female MRL-Mp-lpr/lpr mice spontaneously develop autoimmune disease at three to five months of age and die most commonly from immune complex glomerulonephritis. Kidneys of two-month-old females appeared nearly normal by electron microscopy, and glomerular deposits of IgG an complement component 3 (C3) barely were detectable. In five-month-old females, immunofluorescence revealed numerous deposits of IgG and C3; glomerular mesangial cells were hypertrophic and hyperplastic and contained electron-dense material. There were subepithelial and subendothelial deposits of electron-dense material with swelling of epithelial cell cytoplasm. This disease has many features similar to the immune complex glomerulonephritis observed in New Zealand Black and White hybrid mice and in man.     

Mesangioproliferative Glomerulonephritis in Mink with Encephalitozoonosis

Renal specimens from 6 mink with encephalitozoonosis were studied by light and electron microscopy and immunohistochemistry. The glomeruli of affected kidneys had a mesangioproliferative glomerulonephritis which was characterized by an increase in mesangial cells and matrix in most glomeruli. Some glomeruli were partially or completely sclerosed. There were protein or granular casts in the cortical and medullary tubules. Interstitial nephritis, vasculitis and tubular cysts were found. Electron microscopy demonstrated extensive matrix and increased cellularity in the mesangial areas. Glomeruli showed segmentally thickened or wrinkled capillary basement membranes. Electron dense deposits were found in the glomerular basement membranes and mesangium. Peroxidase-anti-peroxidase immunohistochemistry demonstrated that IgG and IgM positive material was present as granular deposits in the glomerular basement membrane and occasionally in the mesangium.     

Glomerular lesions in renal biopsies of Saimiri boliviensis (primate) examined by light and electron microscopy and immunohistochemistry

In order to determine the existence of glomerular lesions in Saimiri boliviensis, renal biopsies were performed in 20 clinically healthy animals of similar age and both sexes. Biopsies were obtained by laparotomy with a Tru-Cut biopsy needle. Mesangioproliferative glomerulonephritis characterized by an increased number of mesangial cells and increased mesangial matrix was present in 35% of the animals. Proliferative glomerulonephritis characterized by increased numbers of epithelial and endothelial cells with narrowed capillary lumen, and membranous glomerulonephritis characterized by diffuse thickening, wrinkling, and occasional lamellation of basement membranes, were present in 15% of the samples. Ultrastructural features included increased mesangial matrix, fusion of the visceral epithelial foot processes, thickened glomerular basement membranes, and incipient lamellation. Immunohistochemical examination revealed granular deposits of immunoglobulin M in the cytoplasm of mesangial cells and in the mesangial matrix in 50% of the samples.     

Glomerulopathy with IgA deposition in the dog.

In 100 dogs autopsied, glomerular IgA deposition was examined by the immunofluorescence technique and the histopathological features of glomeruli with IgA deposition were examined by light and electron microscopy. The incidence of the IgA deposition was age-related but there were no sex and breed predisposition. Deposition of IgA was observed mainly in mesangial areas in approximately a half (47%) of dogs examined. IgG, IgM and C3 often co-deposited. Histopathology of the glomeruli with IgA deposition indicated increase of mesangial cells, crescent formation, hemispherical deposits in paramesangial areas and glomerular sclerosis. Ultrastructurally electron dense substances positive for IgA deposited in mesangial and paramesangial areas. The examination to know the relation between the severity of IgA deposition and the number of mesangial cells or percent of the cells to total glomerular cells indicated that mesangial cells increased at the early stage of the disease and subsequently epithelial and endothelial cells proliferated as the increasing amount of IgA. Dogs suffering from enteritis or liver diseases showed high incidence of glomerular IgA deposition.     

Atypical membranoproliferative glomerulonephritis in a cat

Membranoproliferative glomerulonephritis was observed in a 2-year-old male Japanese domestic cat with clinical renal failure. In the glomeruli, moderate mesangial hypercellularity with an increased mesangial matrix and thickening of the capillary walls were prominent. In addition, frequent duplication of the capillary walls, splitting, and spike formation were observed in the glomerular basement membrane. Granular cat IgG and complement component deposition were detected globally along the glomerular capillary walls and in the mesangium. Transmission electron microscopy revealed dense deposits in the subendothelial and subepithelial regions and the mesangium. Mesangial interposition was also observed. These glomerular lesions are also found in humans with membranoproliferative glomerulonephritis type III, which has not been reported in animals.     

Immune complex-mediated glomerulonephritis associated with bacterial kidney disease in the rainbow trout (Oncorhynchus mykiss).

Rainbow trout (Oncorhynchus mykiss) developed a post-infectious chronic membranous glomerulonephritis 15 months after they had been experimentally infected with Renibacterium salmoninarum. Histologically, peritubular and periglomerular fibrosis, hypercellular glomeruli with occluded Bowman's space, and partial or complete adhesion to Bowman's capsule were constant features. Electron microscopy revealed thickened glomerular basement membranes with spikes accompanied by finely granular electron-dense deposits at the epithelial side and dense material in the mesangial matrix. Indirect immunofluorescence indicated linear immunoglobulin deposits along the glomerular basement membrane. The presence of R. salmoninarum was demonstrated by culture and by indirect immunofluorescence. Low serum hemagglutination-inhibiting antibody titers were demonstrated.     

Pathological changes in kidneys of dogs with natural Leishmania infection.

A study was made of the nephropathy in canine leishmaniasis produced in ten adult dogs naturally infected with Leishmania infantum. Renal function analyses were performed (uraemia, creatinaemia, plasma proteins, biochemistry and urinary sediment), the humoral immune response (fluorescent antibodies and levels of serum IgG, IgM and IgA) was assessed and histopathological studies were carried out. Correlation of the results showed acute renal insufficiency which was reversible in two animals (endotheliomesangial glomerulonephritis) and irreversible in four cases corresponding to glomerulonephritis in its Type I and Type II proliferative forms; extensive increase in the glomerular basal membrane, proliferation of mesangial cells and growth of the mesangial matrix were observed, as was a widespread incidence of immune complex deposits. Two animals showed chronic renal insufficiency. Lack of renal changes (minimal-changes glomerulonephritis) in two dogs was accounted for in one animal by an almost complete absence of symptoms and in the other by chronic viscerocutaneous symptoms; neither showed more than a slight immunoglobulin response.     

Effects of a Specific Thromboxane Synthetase Inhibitor on Development of Experimental Dirofilaria immitis Immune Complex Glomerulonephritis in the Dog

Twelve Beagle dogs were immunized with aqueous-soluble Dirofilaria immitis antigens, and subsequent to at least fivefold increases in serum antibody titer, 6 mg of homologous antigen was infused into the left renal artery. Six dogs were treated once daily starting the day of infusion with 0.75 mg/kg of 1-benzylimidazole (1-BIM) in saline. Six control dogs were given saline only. Light, immunofluorescent, and transmission electron microscopic examinations of renal tissue from control dogs, 10 days after antigen infusion, showed a mesangioproliferative glomerulonephritis in the left kidney with polymorphonuclear leukocyte (PMNL) infiltration and fibrin deposition. Immunoglobulin (Ig) G, M, C3, and Dirofilaria antigen deposits were observed in a segmental granular pattern. Mesangial, subendothelial, and intramembranous electron dense deposits were observed, and anti-Dirofilaria antibodies were demonstrated in kidney eluates from each dog. Administration of 1-BIM had no significant effect on IgG, IgM, C3, or antigen deposits, electron dense deposits, or concentration of antibody in kidney eluates. However, 1-BIM-treated dogs had less glomerular cell proliferation, periodic acid-Schiff (PAS) positive glomerular staining, PMNL infiltration, and fibrin deposition. These data suggest that thromboxane is an important mediator in the development of immune complex glomerulonephritis, and that in certain circumstances, inhibition of thromboxane synthesis may be an effective therapy for immune complex glomerulonephritis in the dog.     

Membranous glomerulonephritis in dogs infected with Dirofilaria immitis.

Membranous glomerulonephritis was diagnosed in five dogs with patent Dirofilaria immitis infections. Electron-dense deposits were present on the epithelial side of the glomerular basement membrane. An immunofluorescent study demonstrated immunoglobulins in the capillary wall and mesangium of the glomeruli. The glomerular lesions were considered to represent an immune complex form of glomerulonephritis induced by the D. immitis infection.     

Experimental immune complex glomerulonephritis in dogs receiving cationized 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.     

Idiopathic immune complex glomerulonephritis in dogs with multisystem involvement

Renal specimens obtained by biopsy and/or at necropsy from 4 dogs with nephrotic syndrome were studied using light, immunofluorescence, and electron microscopies. The glomerulonephritis observed in these dogs was considered an idiopathic immune complex glomerulonephritis associated with multisystem involvement because causes of glomerulonephritis in these dogs could not be established. Immunoglobulin A was observed in granular deposits in the mesangial and subendothelial regions of the glomeruli. The relationship of the clinical and pathologic features of this disease in dogs to various renal syndromes in human beings are described.     

Kidney ultrastructural lesions in dogs experimentally infected with Dirofilaria immitis (Leidy, 1856)

Kidneys of 16 beagles with experimentally induced heartworm (Dirofilaria immitis) infections and 4 heartworm-nai;ve dogs were studied by light and electron microscopy. The infections were induced either by subcutaneous injection of infective larvae or by the transplantation of adult parasites, and infection periods varied from 111 to 818 days and 365 to 923 days, respectively. One control group of heartworm-na?ve dogs and four groups of heartworm-infected dogs, which were divided according to the type and the length of infection, were used. In the infected dogs, thickening of the glomerular basement membrane (GBM), the presence of dense deposits in the GBM, and foot process effacement were the most frequent lesions observed. In some dogs, electron dense deposits were seen in the GBM and the mesangium and/or enlargement of the mesangial matrix could be characterized. The longer the infection period, the thicker the GBM and the more common the occurrence of foot process effacement. In general, these alterations were more evident in animals that had been infected for more than 1 year, had high microfilaremia, and had 14 or more parasites in the main pulmonary artery and its branches. The presence of dense deposits suggests that the pathogenesis of kidney disease in dirofilariasis is associated with deposits of immune complexes in the membrane. The finding of ultrastructural changes in dogs with early prepatent infections suggests that immature heartworms, as well as microfilariae and possibly adult worms, contribute to the glomerulonephropathy.     

Proteinuria in the dog: a pathomorphological study of 51 proteinuric dogs

Renal cortical biopsies of 51 dogs with spontaneous proteinuria were examined by histology, electron microscopy and immunofluorescence. Glomerular lesions were classified in four groups: mesangioproliferative, membranoproliferative and membranous glomerulonephritis and amyloidosis. The glomerular and the tubulointerstitial lesions were graded, using a semiquantitative system. The results were used for the calculation of correlation coefficients between several parameters. A positive correlation was found between the severity of glomerular and tubulointerstitial lesions. Fibrin detection by immunofluorescence and histochemical methods appeared not to be correlated. The presence of electron dense deposits correlated only with the fluorescence for IgG and C3. Fluorescence for IgA and IgM was frequently observed in cases with or without dense deposits.     

Histopathologic patterns of nephropathy in naturally acquired canine visceral leishmaniasis

Although the nephropathy of visceral leishmaniasis (VL) is known both in humans and dogs, histopathologic alterations have not been thoroughly studied. We examined renal alterations in 55 dogs with naturally acquired VL compared with five noninfected dogs from an endemic area in northeastern Brazil. Glomerulonephritis was found in 55 dogs, interstitial alterations in 53 dogs, and tubular changes in 43 dogs with VL. The glomerular alterations found were minor glomerular abnormalities (n = 8, 14.5%), focal segmental glomerulosclerosis (n = 10, 18.2%), mesangial proliferative glomerulonephritis (n = 17, 32.7%), membranoproliferative glomerulonephritis, (n = 18, 30.9%), crescentic glomerulonephritis (n = 1, 1.8%), and chronic glomerulonephritis (n = 1, 1.8%). Morphometric and ultrastructural studies complemented the analysis. The five control animals exhibited no glomerular alterations. The glomerular lesions were related to functional alterations. Considering that the alterations of canine and human nephropathy in VL are very similar, the data obtained in this study constitute an important contribution to the understanding of canine and human VL nephropathy.     

Spontaneous early-onset glomerulonephritis in a 8-week-old male Crj:CD1 (ICR) mouse

Glomerular lesions including membranoproliferative glomerulonephritis occur spontaneously in aged mice, but they are rare in young animals. In our laboratory, spontaneous glomerulonephritis was observed in an 8-week-old male Crj:CD1 (ICR) mouse. Macroscopically, the bilateral kidneys were discolored, but no edema or ascites was observed. Glomerular lesions were characterized by a thickening of capillary walls, a double-contoured basement membrane and mesangial expansion due to increased amounts of matrix. Ultrastructurally, mesangial interposition in the capillary wall and subendothelial deposition of basement membrane-like material were observed. No evidence of immune complex deposition or amyloid was found. On the basis of the observed clinical pathology and histopathology, a secondary form of glomerular lesion was excluded. The glomerular lesion was compatible with glomerulonephritis in a young Crj:CD1 (ICR) mouse.     

Spontaneous mesangiocapillary glomerulonephritis in Finn cross lambs from Alberta.

A spontaneous mesangiocapillary glomerulonephritis occurred in three, one to three month old Finnish Landrace cross lambs from a flock in northern Alberta. The ram was a purebred Finn sheep, and the ewes were Finn-Rambouillet and Finn-Suffolk-Rambouillet crosses. The lambs were found dead without previous clinical signs. Histologically there was marked thickening of glomerular capillary basement membranes, proliferation of mesangial cells, and peri-glomerular fibrosis. An interstitial infiltration of plasma cells and lymphocytes was present with occasional tubular degeneration and proteinaceous cast formation. Focal leukoencephalomalacia was present in one lamb. Electron microscopy demonstrated deposition of electron-dense deposits in a subendothelial location with occasional fusion of overlying foot processes in glomerular capillaries. Indirect immunofluorescence studies demonstrated positive staining material in glomerular capillary walls. These findings in Finnish Landrace cross lambs are characteristic of mesangiocapillary glomerulonephritis, a condition heretofore not reported in North America.     

Glomerular lipidosis accompanied by renal tubular oxalosis in wild and laboratory-reared Japanese rock ptarmigans (Lagopus mutus japonicus)

Glomerular lipidosis is a disease characterized by lipid accumulation in mesangial cells but that has not been fully investigated in avian species. We examined four wild and two laboratory-reared Japanese rock ptarmigans (Lagopus mutus japonicus)--an endangered avian species--presenting vacuolar deposits in the glomeruli. All cases had vacuolar deposits in the glomeruli. In the wild cases, fewer than 30% of all glomeruli were affected, compared with more than 90% in the laboratory-reared cases. In the wild cases, most deposits were mild and restricted to the mesangial areas of glomeruli. In the laboratory-reared cases, nearly all of the deposits covered entire glomeruli. Electron microscopy of mild deposits revealed vacuoles in the cytoplasm of mesangial cells. These vacuoles were positive for Sudan III, Sudan black B, oil red O, Nile blue, periodic acid-Schiff, Schultz test, and digitonin stain and were negative for performaric acid-Schiff stains. Based on these results, we diagnosed the glomerular lesion as glomerular lipidosis caused by uptake of low-density lipoprotein in mesangial cells. Except for one wild case, all cases exhibited renal tubular oxalosis. The severity of tubular oxalosis tended to be related to the severity of glomerular lipidosis: In cases of mild glomerular lipidosis, tubular oxalosis was also mild or absent. We therefore diagnosed the primary lesion as glomerular lipidosis accompanied by tubular oxalosis. The four wild cases came from different zones and therefore had no opportunities to interbreed and no common relatives. We believe these data support the hypothesis that glomerular lipidosis is a disease of the general population ofJapanese rock ptarmigans. This is the first report of glomerular lipidosis accompanied by renal tubular oxalosis in an avian species.     

Systemic necrotizing vasculitis and glomerulonephritis in grower pigs in southwestern Quebec.

This purpose of this study was to describe the clinical features and the pathological findings of an unusual condition observed in pigs of a fattening unit in southwestern Quebec. Two of these pigs were submitted for complete postmortem examination. The disease was characterized by a systemic necrotizing vasculitis and an exudative and proliferative glomerulonephritis. In the skin, the vascular lesions produced a conspicuous papular dermatopathy with a characteristic distribution. Bacteriological and virological results were inconclusive. In the glomeruli, there were extensive granular complement deposits with scattered immunoglobulin M. Transmission electron microscopy did not reveal any dense deposits in glomerular basement membrane. The cause of this newly recognized and potentially lethal condition remains unknown, although histological and immunopathological observations suggest an immune-mediated process.     

Glomerular lesions associated with proteinuria in clinically healthy dogs.

Spontaneous proteinuria in otherwise clinically normal adult Beagles 4-6 years old was studied for 2 years. Eighteen dogs, representing a population of 218 Beagles, were placed into three groups: group I, nonproteinuric; group II, intermittently proteinuric; group III, persistently proteinuric. The groups were alike on the basis of laboratory tests, except urinary protein loss. Proteinuria was persistent in most affected dogs but not progressive during the 2 years. The loss of proteins with high molecular weight, including alpha-, beta-, and gamma-globulins, suggested the proteinuria was of glomerular origin. There were glomerular lesions but no other significant change in the kidneys and urogenital system. Lesions were generalized and characterized by prominent, local or diffuse mesangial proliferation and by thickening, wrinkling, and splitting of the glomerular basement membrane. The subendothelial space was often widened and contained electron-dense deposits. Similar electron-dense deposits, as well as lipid and mineral, were in the mesangium. Alterations in visceral epithelial cells and endothelium were prominent. Periglomerular sclerosis was present but tended not to correlate with the severity of mesangial change in any given renal corpuscle. The severity of both mesangial and periglomerular changes increased with increasing proteinuria. Immunofluoescence studies demonstrated granular discontinuous localization of IgG and betaIC-globulins in the glomerular capillaries and mesangium. Similar localization was seen but to a lesser extent in nonproteinuric dogs. The glomerular lesions seen in these clinically healthy, proteinuric dogs are similar to those described in various canind diseases associated with terminal renal failure.     

Localization of proliferative and apoptotic cells in the kidneys of ICR-derived glomerulonephritis (ICGN) mice

The ICR-derived glomerulonephritis (ICGN) mouse is a novel inbred mouse strain with a hereditary nephrotic syndrome, considered to be a good model of human idiopathic nephrotic syndrome and develops proteinuria, hypoproteinemia and anemia. In the present study, we compared the cell kinetics in the kidneys of ICGN mice with age-matched ICR mice as normal controls. The proliferating cells were visualized by 5-bromo-2'-deoxyuridine labeling, and apoptotic cells were determined by terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end-labeling. Many proliferating epithelial cells of renal tubules, glomerular mesangial cells and tublointerstitial fibroblast-like cells were observed in the kidneys of ICGN mice, but no proliferating cells were seen in the kidneys of ICR mice. Apoptotic cells had round nuclei, and were observed only in the tubulointerstitium in the kidneys of ICGN mice but not in that of controls. The proliferation of renal tubular epithelial cells may represent a compensatory response, and that of mesangial and fibroblast-like cells may play a pathogenic role in nephrotic syndrome. Apoptosis in tubulointerstitial cells with round nuclei may have been erythropoietin-producing cells, and probably caused anemia.