Murine cytomegalovirus glomerulonephritis: clinical and ultrastructural observations.

This investigation was initiated to study and correlate the clinical and ultrastructural aspects of glomerulonephritis induced in the laboratory mouse by the intraperitoneal injection of a sublethal dose of murine cytomegalovirus. An attempt was made to ascertain the pathogenesis of the glomerular changes and the resultant viremia. Murine cytomegalovirus infection caused an acute transient glomerulonephritis in young female mice of the HA/ICR strain. Mice that survived a sublethal inoculation of homogenized infected gland developed transient proteinuria and excreted tubular casts. The murine cytomegalovirus infection resulted in a glomerular lesion that was selective for the mesangial cell. After entering the mesangial cell by phagocytosis the virus replicated in the nucleus and was excreted into the channel of the mesangial matrix, with extension toward the periphery of the capillary loop and adjacent to the urinary space. Virus particles were rarely found in the glomerulus after the 5th day of infection and chronic renal disease was not observed.     

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.     

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.     

Canine glomerulonephritis: new thoughts on proteinuria and treatment

Glomerular disease in the dog is not only a common form of renal disease but also an important cause of chronic renal failure. The presence of immune complexes in glomerular capillary walls is a major cause of canine glomerular disease and is commonly referred to as glomerulonephritis. Leakage of plasma proteins, principally albumin, across the damaged glomerular capillary walls results in persistent proteinuria--the clinicopathological hallmark of glomerulonephritis. Recent evidence suggests that, in addition to being a marker of disease, persistent proteinuria is associated with progressive glomerular and tubulointerstitial lesions and loss of additional nephrons. Perhaps the best treatment for glomerulonephritis is the identification and correction of any underlying inflammatory, immune-mediated or neoplastic disease that results in the deposition or formation of glomerular immune complexes. In cases of idiopathic glomerulonephritis, angiotensin-converting enzyme inhibitors have been shown to decrease proteinuria and potentially slow disease progression.     

Glomerular lesions in dogs infected with Leishmania organisms

OBJECTIVE: To histologically identify glomerular lesions in dogs infected with Leishmania organisms. ANIMALS: 41 dogs (17 sexually intact males and 14 sexually intact and 10 ovariohysterectomized females) that had positive results when tested for leishmaniosis as determined by use of serologic evaluation (indirect fluorescent antibody test, titers of 1:80 to 1:640) and direct microscopic identification of the protozoal organisms. PROCEDURE: Urine samples were collected by use of cystocentesis and examined by qualitative SDS-agarose gel electrophoresis (AGE). All dogs had non-selective (glomerular) or mixed (glomerular and tubular) proteinemia. Specimens were obtained from each dog during ultrasound-assisted renal biopsy and used for histologic examination. Each specimen was stained with H&E, periodic acid-Schiff, Goldner's trichrome, methenamine silver, and Congo Red stains. Specimens were adequate for evaluation when they contained at least 5 glomeruli/section, except for specimens stained with Congo Red in which 1 glomerulus/section was adequate. RESULTS: Examination of renal biopsy specimens revealed various glomerular lesions in all dogs and interstitial or tubular (or both) lesions in 23 of 41 (55%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Glomerular lesions that develop in dogs during infection with Leishmania organisms can be classified histologically as mesangial glomerulonephritis, membranous glomerulonephritis, membranoproliferative glomerulonephritis, and focal segmental glomerulonephritis. Tubulointerstitial histopathologic conditions were not observed as the primary lesion, despite being evident in 23 of 41 (55%) dogs. Use of SDS-AGE for qualitative evaluation of proteinuria and successive collection of specimens during renal biopsies following diagnosis of nonselective glomerular proteinuria provides the possibility for early identification of renal lesions.     

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.     

Spontaneous Glomerular and Tubulointerstitial Lesions in Common Marmosets (Callithrix jacchus)

Spontaneous progressive nephropathy dominated by glomerular lesions in common marmosets has been reported. However, the histopathologic characteristics, including the relationship between glomerular and tubulointerstitial lesions, have not been described in detail. In the present study, the authors examined the histopathologic characteristics of the background renal lesions in common marmosets (3 males and 9 females, 3 to 8 years old). The severity of glomerular lesions was graded into 3 classes: grade I, no alteration; grade II, hilar/focal increase of mesangial matrix; grade III, global/diffuse increase of mesangial matrix. Tubulointerstitial lesions (tubular regeneration and hyperplasia and interstitial inflammation and fibrosis) were scored according to the area of each lesion. The renal lesions were characterized by enlargement of glomeruli, expanded mesangial area with increase of periodic acid-Schiff reaction-positive matrix, tubular regeneration and hyperplasia, and interstitial inflammation and fibrosis. Glomerular lesions progressed with increasing mesangial matrix and aging. Additionally, the tubulointerstitial lesions became exacerbated with progressing glomerular lesions. Tubular hyperplasia was divided into 4 types according to the structure of the cell layer (simple or stratified-like), the area of increased lining cells (partial or entire), cytoplasmic staining (eosinophilic or basophilic), brush border and thickness of basement membrane, and the activity of cell proliferation. In conclusion, the background renal lesions in common marmosets were characterized by glomerular lesions with increase of mesangial matrix, which progressed with aging, and secondary tubulointerstitial lesions, including tubular hyperplasia. Those lesions were thus diagnosed as progressive glomerulonephropathy in common marmosets.     

Liquoid-induced renal lesions in the dog

The role of fibrin in the pathogenesis of renal glomerular scarring in the dog was studied. Fibrin deposition, resulting from disseminated intravascular coagulation, was induced by intravenous injection of Liquoid (sodium polyanethol sulphonate). Thirty-eight puppies were killed from 30 minutes to 39 days after treatment, and the renal lesions examined by light, electron and immunofluorescence microscopy. The major acute lesions in the glomeruli were capillary thrombosis, mesangial and endothelial cell swelling and phagocytosis of fibrin, polymorphonuclear leukocyte infiltration and necrosis. Animals that recovered from this acute phase had focal glomerular scars. Affected glomeruli showed combinations of mesangial enlargement, focal tuft hypercellularity, collagen formation, thickening, wrinkling and duplication of the glomerular basement membranes, and some capsular adhesions. These observations indicate that fibrin deposition can be an important mechanism in glomerular scarring in the dog.     

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.     

Spontaneous ovarian choriocarcinoma in a young ICR mouse

This paper describes the spontaneous ovarian choriocarcinoma observed in a young female Crl:CD1 (ICR) mouse. The mouse was sacrificed at 8 weeks of age after oral administration of a compound for 2 weeks. The left ovary was found to be cystically enlarged with dark red hemorrhaging. The cystic mass contained abundant blood plasma and erythrocytes. At the peripheral regions of the mass, large pleomorphic tumor cells with bizarre shaped nuclei were detected. Tumor cells contained a single large nucleus and abundant eosinophilic to amphophilic cytoplasm. Histopathology of the tumor cells resembled that of trophoblastic giant cells. Therefore, the observed ovarian lesion was diagnosed as a choriocarcinoma. No microscopic lesions were observed in the right ovary or other reproductive organs. Ovarian choriocarcinoma was considered to be of non-gestational origin. This is the first report of ovarian choriocarcinoma in a young ICR mouse.     

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.     

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.     

Glomerulonephritis associated with simultaneous canine adenovirus-1 and Dirofilaria immitis infection in a dog

This article describes a case of glomerulonephritis and immunocomplex (IgM, IgG and C3c) deposition in the mesangium and basement membranes of a 2-year-old dog with canine viral hepatitis and dirofilariasis. The deposits observed in the mesangium were in the vicinity of cells with viral replication. However, no clear relationship was found between viral replication and the deposition of immunocomplexes in the glomerular capillary basement membranes, which may be the reason why these deposits have only been tentatively related to the concomitant infestation by Dirofilaria immitis.     

Glomerulonephritis Associated with Simultaneous Canine Adenovirus‐1 and Dirofilaria immitis Infection in a Dog

This article describes a case of glomerulonephritis and immunocomplex (IgM, IgG and C3c) deposition in the mesangium and basement membranes of a 2‐year‐old dog with canine viral hepatitis and dirofilariasis. The deposits observed in the mesangium were in the vicinity of cells with viral replication. However, no clear relationship was found between viral replication and the deposition of immunocomplexes in the glomerular capillary basement membranes, which may be the reason why these deposits have only been tentatively related to the concomitant infestation by Dirofilaria immitis.     

Investigation of glomerular lesions in dogs with acute experimentally induced Ehrlichia canis infection.

Six male Beagles were inoculated with Ehrlichia canis. Transient proteinuria was confirmed during the acute phase of infection by serial determination of urinary protein-to-creatinine ratio. Peak urine protein loss, consisting principally of albumin, was observed 2.5 to 3.5 weeks after inoculation. Renal biopsy specimens were obtained before inoculation, during peak proteinuria, and 10 weeks after inoculation when proteinuria had resolved. Renal tissue was evaluated by use of light, immunofluorescent, and electron microscopy to correlate specific glomerular lesions with development of proteinuria. Histologic examination revealed perivenular and interstitial infiltrates of lymphocytes and plasma cells localized principally to the renal cortex. Glomerular lesions were minimal to absent. Immunofluorescent staining revealed moderate to marked deposition of anti-canine IgG and IgM in the glomerular tufts and mesangium. Depositions of anti-canine complement factor C3 were not observed. Immunofluorescent staining persisted 10 weeks after inoculation, despite resolution of proteinuria, and probably represented passive trapping of immunoglobulins. Ultrastructural examination revealed fusion of podocyte processes that coincided with development of proteinuria. Electron-dense deposits or changes in the basement membrane were not observed. Morphometric measurements of average podocyte process length and percentage of coverage of basement membrane by podocyte processes were used to quantify the degree of process fusion. Both measurements increased significantly (P < 0.05) during peak proteinuria, and returned to preinoculation values when proteinuria had resolved 10 weeks after E canis inoculation. These findings indicated possible minimal-change glomerulopathy, rather than immune-complex glomerulonephritis, during acute E canis infection and could explain transient proteinuria without histologic evidence of glomerular disease.     

Immunoglobulin-A nephropathy with crescentic glomerulonephritis in a pigtailed macaque (Macaca nemestrina)

A 4-year-old female pigtailed macaque (Macaca nemestrina), experimentally coinfected with simian immunodeficiency virus (SIVmac251) and Mycobacterium bovis(bacillus Calmette-Guerin), was euthanatized 1 year after infection because of weight loss and labored breathing. On gross examination, both kidneys were found to be markedly enlarged (right: 54.7 g and left: 51.7 g; normal < 20 g). Renal lesions were evaluated by histopathologic, immunohistochemical, and ultrastructural methods. Light microscopy revealed that the glomeruli were diffusely hypercellular with expansion of the mesangial matrix, and crescent formation affected approximately 60% of the glomeruli. By immunohistochemical evaluation, it was found that the crescents were composed principally of macrophages, as seen by CD68 (KP1), MRP8, MAC387, and HAM56 expression. Electron microscopic examination of the glomeruli revealed extensive intramembranous, subendothelial, and mesangial electron-dense deposits and multifocal fusion of the visceral epithelial foot processes. Immunofluorescence, used to determine the composition of the electron-dense deposits, revealed diffuse granular mesangial and capillary staining for immunoglobulin A (IgA). The renal changes described in this case report are most consistent with the findings of crescentic gloerulonephritis with IgA immune complex deposition in the glomerular basement membrane and mesangium as described in humans with IgA nephropathy.     

The Kidneys of Infant Mice are not Sensitive to the Food Mycotoxin Contaminant Nivalenol

Nivalenol (NIV) is a trichothecene mycotoxin produced by Fusarium fungi that frequently contaminates agricultural commodities. Dietary administration of NIV to adult mice affects the renal glomeruli, but data about NIV toxicity in human infants are limited. To evaluate the effects of NIV on infant kidneys, 3-week-old male ICR-derived glomerulonephritis (ICGN) and ICR mice were administered 0, 4, 8 or 16 ppm NIV in diet for 4 weeks, and their renal status was compared with age-matched or adult ICR mice. In ICGN mice, the number of glomeruli showing mesangial expansion and α-smooth muscle actin (SMA)-positive mesangial cells was higher with 16 ppm NIV compared with controls. No other significant differences were observed in ICGN mice. In infant ICR mice, the IgA serum concentrations were significantly elevated without glomerular morphological changes in the 16 ppm NIV group. There was no difference in NIV sensitivity in the kidneys of infant ICGN and ICR mice. These data suggest that the kidneys in infant mice are not sensitive to nivalenol under the present conditions.     

Glomerular lesions in unilateral nephrectomized and diabetic (UN-D) mice.

Experimental diabetes was induced in both control and unilaterally nephrectomized male mice by injecting streptozotocin (SZ) (50 mg/kg x 5 days) one week after nephrectomy. The time course changes in the glomerular lesions were examined for up to 12 weeks after completion of the SZ-injection (12WAI). In unilateral nephrectomized and diabetic mice, mild segmental expansion of the mesangial area developed at 4WAI, and it progressed to prominent segmental glomerulosclerosis at 12WAI. In the electron microscopic examination at 12WAI, marked expansion of the mesangial area, segmental thickening of the glomerular basement membrane, fusion of the foot processes of podocytes and a prominent increase in the number of microvilli of capillary endothelial cells were observed. On the other hand, mild to moderate expansion of the glomerular mesangial area was only sporadically found in unnephrectomized diabetic mice at 12WAI. Interestingly, Bowman's capsules of diabetic mice were generally lined with flattened epithelia but those of non-diabetic mice with cuboidal or low columnar epithelia.     

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.     

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.