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.     

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.     

Abnormal distribution of anionic sites in the glomerular basement membrane in glomerulonephritis of dogs infected with Dirofilaria immitis

Ultrastructural alteration of anionic sites (ASs) in the glomerular basement membrane (GBM) was studied in glomerulonephritis characterized by linear capillary IgG deposition in four dogs infected with Dirofilaria immitis and two normal control dogs using polyethyleneimine. ASs were identified as small dense particles distributed regularly in the lamina rara externa (LRE), but there were no ASs in the lamina densa (LD) of the GBM of the control dogs. In the glomeruli of the infected dogs, ASs were distributed regularly or irregularly in the thickened LD. ASs were in addition localized over the characteristic continuous bands of subendothelial dense deposits. The number of ASs of the LRE increased in all four infected cases as compared to the controls (p<0.01).     

Renal microcirculatory and correlated histologic changes associated with dirofilariasis in dogs

Nine 7-month-old Beagle dogs were inoculated with 200 third-stage larvae of Dirofilaria immitis. The development of cardiac disease secondary to heartworm infection was confirmed by thoracic radiography, echocardiography, and angiography with blood pressure measurements. The only indication of renal disease was mild-to-moderate proteinuria. The dogs were euthanatized approximately 18 months after inoculation. The mean microfilarial count in blood at the time of euthanasia was 88,700/ml, with a mean of 89 adult heartworms in the vena cavae, heart, and pulmonary arteries. The kidneys were perfused for microangiographic and correlative histologic examination of the intrarenal microvasculature and associated renal morphologic features. Angiograms of whole kidneys from 6 dogs revealed attenuation or truncation of the major renal vessels. Microangiograms of all kidney slices revealed attenuation in the microangiographic appearance of the glomerular capillaries. Histologic examination of all kidney slices revealed mild-to-intense, diffuse, chronic interstitial nephritis and generalized membranoproliferative glomerulonephritis. Microfilariae were observed within the glomerular capillaries and the medullary vessels. The microangiographic changes correlated with and were explained in part by the histologic changes in the renal parenchyma.     

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.     

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.     

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.     

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.     

Disseminated coccidioidomycosis in a captive Indochinese tiger (Panthera tigris corbetti) with chronic renal disease.

A 19-yr-old, 78.2-kg captive female Indochinese tiger (Panthera tigris corbetti) from the El Paso Zoo (El Paso, Texas, USA) with chronic renal disease was euthanized after a 10-day course of anorexia, depression, progressive rear limb weakness, muscle fasciculations, and head tremors. Postmortem findings included pericardial effusion, generalized lymphadenopathy, glomerulosclerosis, glomerular atrophy with membranous glomerulonephropathy, and pancreatic adenocarcinoma. Pyogranulomatous pneumonia, pericarditis, and lymphadenitis were associated with fungal spherules histomorphologically consistent with Coccidioides immitis. Rising antibodies to C. immitis were detected on samples obtained perimortem and 2 mo before euthanasia. Retrospective serology was negative for two additional Indochinese tigers, two Iranian leopards (Panthera pardus saxicolor), two jaguars (Panthera onca), two bobcats (Lynx rufus texensis), two ocelots (Leopardus pardalis), and three Amur leopards (Panthera pardus orientalis) housed at the zoo over an 8-yr period. Despite being located within the endemic region for C. immitis, this is only the second case of coccidioidomycosis reported from this institution.     

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.     

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.     

Effects of thromboxane synthetase inhibition on immune complex glomerulonephritis.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histological changes associated with immune complex glomerulonephritis.     

High incidence of glomerulonephritis associated with inclusion body hepatitis in broiler chickens: routine histopathology and histomorphometric studies

During the routine histologic evaluation of an outbreak of inclusion body hepatitis (IBH) in Mississippi broilers, a high incidence of renal enlargement and glomerulonephropathy was observed in the birds presenting classic hepatic pathology. Characteristic intranuclear adenoviral inclusion bodies were demonstrated in the livers of these birds, and fowl adenovirus was identified by viral isolation and by PCR. The glomerular lesions were consistent with proliferative or membranoproliferative forms of glomerulonephritis. Histomorphometric evaluations were performed to generate a more quantitative analysis of altered glomerular size and cellularity, to detect statistically significant borderline changes, and to get a clearer insight into the incidence of the glomerular alterations. Marked increases in both the average glomerular size (area) and the total glomerular cellularity were observed for the affected glomeruli relative to normal controls. The average glomerular area values for normal glomeruli in the peripheral subcapsular cortical and central cortical kidney regions were 1791 microm2 and 5302 microm2, respectively. In contrast, glomerular measurements for kidneys exhibiting glomerulonephritis by routine histopathology, had average values for the two regions of 4429 microm2 and 11,063 microm2. The average glomerular cell counts for the two regions in controls were 44 and 107 cells/ glomeruli, while averages for birds with glomerulonephritis were 85 and 193 cells/glomeruli. The proportion of IBH-associated glomeruli greater than two standard deviations above the mean glomerular size of the normal controls was 52% for the central region and 62% for the peripheral region.     

Ovine mesangiocapillary glomerulonephritis type I and crescent formation

Morphologic examination of four Finnish Landrace mixed-breed lambs, 27 to 35 days of age, affected with mesangiocapillary glomerulonephritis type 1, demonstrated a progressive glomerulonephritis. By 27 days of age, three lambs had crescents in 58 to 93% of glomeruli. These three lambs were also uremic. The accelerated rate of crescent formation was attributed to infiltrating polymorphonuclear leukocytes and monocytes, the result of discontinuities (gaps) in the glomerular basement membrane, and to the loss of the integrity of Bowman's capsule. In the three lambs, platelets were identified adjacent to the endothelium or denuded glomerular basement membrane. Two distinctly different types of crescents were noted, apparently dependent on the integrity of Bowman's capsule. One type resulted from the influx of inflammatory cells and dissociation of parietal epithelial cells from Bowman's capsule. The other type was more extensive and contained collagen and was associated with damage to Bowman's capsule resulting in cellular infiltration from the interstitium and sclerosis. Based on morphologic similarities, ovine mesangiocapillary glomerulonephritis is a suitable model for studying the pathogenesis and treatment of mesangiocapillary glomerulonephritis type 1 in human beings.     

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.     

Electron microscopic structure of mesangioproliferative glomerulonephritis (MesPGN) in animals

In a murine lupus model, the kidneys of 42 MRL mice of different age groups (substrains MRL/Mp-lpr/lp and -+/+) were studied by light and transmission electron microscopy. The results demonstrate the ultrastructural feature of the mesangial-proliferative glomerulonephritis which is one of the observed forms of glomerulonephritis. The most important alterations are a severe proliferation of mesangial cells (with an increase in rough endoplasmic reticulum and mitochondria) and electron dense deposits in different sites of the glomerular basement membrane (subepithelial, subendothelial, intramembranous). These deposits are proposed to be immune complexes. Osmiophilic intracytoplasmic inclusions of the mesangial cells are indications of an altered renin production. Alterations of the glomerular epithelial cells are characterized by fusions of the epithelial pedicles, an increase of microvilli and intracytoplasmic concentrations of electron dense material which are also proposed to be immune complex deposits. The morphological feature of the mesangial-proliferative glomerulonephritis is completed by an activation and focal edema of endothelial cells. The described alterations are discussed and compared with findings in other species.     

水貂脑胞内原虫病肾小球病理形态学研究

用光学、电子显微镜和免疫组织学方法对6只患有脑胞内原虫病的水貂肾脏进行了研究。结果表明,脑胞内原虫感染可引起水貂系膜增生性肾小球肾炎,其发生与免疫复合物颗粒在肾小球基膜和系膜区的沉积有密切关系。     

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.