Spontaneous glomerulonephritis in dogs. II. Correlation of glomerulonephritis with age, chronic interstitial nephritis and extrarenal lesions

A morphologic study of 103 dogs, including two with renal amyloidosis, showed that different types of diffuse glomerulonephritis are correlated with different age groups. Membranous and membranoproliferative glomerulonephritis were more common in middle-aged and older animals, whereas mesangial lesions were found predominantly in younger dogs and considered to be early glomerular changes. Glomerulonephritis largely occurred independently of interstitial nephritis. The incidence of interstitial lesions was 71%. Chronic interstitial nephritis was rare in dogs under 1 year old. Glomerulonephritis did not seem to induce interstitial nephritis. Glomerulonephritis occurred not only in kidneys with severe interstitial damage, but also in those with slight damage. The indicated that glomerulonephritis occurred independently of interstitial nephritis. In end-stage kidneys with severe fibrosis, mesangial changes seemed to predominate.     

Spontaneous systemic hypertension in dogs: five cases (1981-1983)

Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that were examined because of apparent blindness caused by intraocular hemorrhage and/or retinal detachment. Secondary causes of hypertension, including renal, adrenal, and thyroid disease, were investigated. Four of the dogs had glomerulonephropathy, renal insufficiency, and proteinuria. Four dogs had compensatory cardiac hypertrophy. Hypertension in 4 of 5 dogs was associated with glomerulosclerosis with chronic renal insufficiency, bilateral adrenocortical hyperplasia, adrenocortical adenoma with renal amyloidosis, and immune-mediated glomerulonephritis with chronic renal insufficiency, respectively. The fifth dog was determined to have essential hypertension. The dogs were treated for their primary diseases. Sodium restriction alone was inadequate to reduce blood pressure; 4 of the dogs also required antihypertensive medications.     

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.     

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.     

Effects of allopurinol treatment on the progression of chronic nephritis in Canine leishmaniosis (Leishmania infantum)

Forty dogs with canine leishmaniosis (CL) participated in this study, which was designed to investigate the effect of allopurinol on the progression of the renal lesions associated with this disease. The animals were allocated into 5 groups. Group A dogs (n = 12) had neither proteinuria nor renal insufficiency, group B dogs (n= 10) had asymptomatic proteinuria, and group C dogs (n = 8) were proteinuric and azotemic. Two more groups, CA and CB, comprising 5 dogs each, served as controls for groups A and B, respectively. Group A, B, and C dogs received allopurinol PO (10 mg/kg q12h) for 6 months, whereas group CA and CB dogs were placebo-treated. Serum biochemistry profile, urinalysis, urine protein/creatinine ratio, and glomerular filtration rate (GFR) measurements were carried out at the beginning of the study, the 3rd month, and the 6th month, whereas renal biopsies were carried out only at the beginning and the end of the trial. Membranoproliferative glomerulonephritis was the most common cause of chronic renal failure. Mesangioproliferative and tubulointerstitial nephritis were detected even in group A and CA dogs. Allopurinol not only lowered proteinuria in group B dogs but also prevented the deterioration of GFR and improved the tubulointerstitial, but not the glomerular, lesions in both group A and group B dogs. Further, it resolved the azotemia in 5 of the 8 dogs admitted with 2nd stage chronic renal failure (group C). Consequently, treatment with allopurinol is advisable in CL cases with asymptomatic proteinuria or 1st-2nd stage chronic renal failure.     

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.     

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.     

Chronic renal failure in dogs: a comparative clinical and morphological study of chronic glomerulonephritis and chronic interstitial nephritis.

Chronic renal disease is an important clinical problem in dogs. Until recently, diffuse renal fibrosis with chronic renal failure has been attributed mainly to chronic interstitial nephritis, itself considered to be the end stage of acute leptospiral nephritis. A clinical and morphological analysis of eight cases of chronic glomerulonephritis is described and a comparison made with eight dogs suffering from severe chronic interstitial nephritis. Clinically and biochemically, the two diseases were virtually indistinguishable, both resulting in uraemia. A possible distinguishing feature of chronic interstitial nephritis was the anaemia which was absent from chronic glomerulonephritis cases. Morphologically, the two diseases appeared to be distinguishable on three grounds; the pattern and severity of fibrosis, the degree of fibrin deposition and the immunofluorescence findings.     

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.     

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.     

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.     

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.     

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.     

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.     

Detection of Leishmania infantum DNA by fret-based real-time PCR in urine from dogs with natural clinical leishmaniosis

The aim of this study was to detect Leishmania infantum DNA by real-time PCR in urine from different groups of dogs with clinical leishmaniosis. Urine from 10 clinically healthy dogs and 43 dogs with clinical leishmaniosis diagnosed by positive serology and/or bone marrow PCR were studied. The group of 43 dogs with clinical leishmaniosis was divided into three subgroups: 13 dogs with renal insufficiency and proteinuria (urine protein-creatinine ratio greater than one), 13 dogs with only proteinuria, and 17 dogs with neither renal insufficiency nor proteinuria. The detection of Leishmania DNA was performed by light cycler real-time PCR using hybridization probes in each urine sample. Leishmania positive PCR was found in 47% (20/43) of the urine from leishmaniotic dogs, while all urine from clinically healthy dogs were negative. The percentages of positive Leishmania PCR were 85% (11/13) in dogs with renal insufficiency and proteinuria, 23% (3/13) in dogs with proteinuria and 35% (6/17) in dogs with neither renal insufficiency nor proteinuria. Dogs with renal insufficiency and proteinuria presented a statistical significant greater percentage of positive Leishmania PCR in urine when compared with the other subgroups (P<0.02). This study demonstrates the presence of Leishmania DNA in urine of dogs with leishmaniosis. Those dogs with severe renal damage present a greater number of Leishmania parasites in urine.     

Peritoneal dialysis in dogs and cats: 27 cases (1976-1987)

The records of 25 dogs and 2 cats treated with peritoneal dialysis during an 11-year period were evaluated. The indications for peritoneal dialysis were acute renal failure in 21 animals, chronic renal failure in 5 animals, and azotemia of undetermined cause in 1 animal. Peritoneal dialysis resulted in a significant (P less than 0.05) decrease in serum urea nitrogen concentration in 19 of the dogs and a significant (P less than 0.05) decrease in serum creatinine in 20 dogs. The most common complication of peritoneal dialysis was hypoalbuminemia (11 animals affected). Other common complications were dialysate retention/catheter obstruction (8 animals), peritonitis (6 animals), hypochloremia (6 animals), and subcutaneous leakage of dialysate (6 animals). Twelve dogs and 2 cats died during treatment, 6 dogs were euthanatized, and 1 dog was lost to follow-up evaluation. The remaining 6 dogs survived and were discharged from the hospital after successful peritoneal dialysis. On the basis of the results of this study, the authors concluded that peritoneal dialysis, although associated with a high complication rate, was a successful technique for reducing azotemia in dogs with acute and chronic renal failure. Survival rates were poor because of the severity of the underlying renal diseases.     

Humoral and cellular immune responses against Type I cysteine proteinase of Leishmania infantum are higher in asymptomatic than symptomatic dogs selected from a naturally infected population

Canids are natural reservoirs of Leishmania infantum and have been promoted as experimental hosts to decipher the pathogenesis of human visceral leishmaniasis (VL). In this study, the presence of IgG antibodies as well as the presence of mononuclear leukocytes reactive to different cysteine proteinases (CPs) were examined in 13 L. infantum-infected dogs (six with symptoms, seven asymptomatic). Cysteine proteinases which belong to papain-like enzymes known as clan CA are the most studied CPs of parasite protozoa. These molecules are expressed by the intracellular stages of the parasite and could be immunogenic. We studied Type II CP (CPA) and Type I CP (CPB) with its long C-terminal extension (CTE) which could be highly immunogenic. We showed that the level of antibodies reactive to rCPA is low in both symptomatic and asymptomatic dogs. In contrast, when CPB and CTE were used as antigens, the level of total IgG (with IgG2 superior to IgG1) reached higher values in asymptomatic dogs than in dogs with VL. While the peripheral blood mononuclear cell (PBMC) reactivity was significant when cultured in the presence of freezed/thawed (F/T) lysate, it remained low in presence of CP although always higher for PBMC recovered from asymptomatic dogs. We showed the importance of CPB and CTE in particular as a target of immune response and their potential use for serodiagnosis in asymptomatic dogs.     

Clinicopathologic, renal immunofluorescent, and light microscopic features of glomerulonephritis in the dog: 41 cases (1975-1985)

In a 10-year retrospective study, we evaluated the clinicopathologic features and renal immunofluorescence patterns of glomerulonephritis in 41 dogs. On the basis of results of histologic examinations, the dogs were segregated into 3 groups, including membranous (n = 12), mesangioproliferative (n = 15), or membranoproliferative glomerulonephritis (n = 14). No significant differences existed among groups in regard to age or duration of illness. Most dogs had been ill for one month or longer. The proportion of dogs with azotemia, anemia, and hyperphosphatemia were not different among the disease groups. Proportion of dogs with hypoalbuminemia and the severity of hypoalbuminemia were not different among groups. Highest urine protein losses and 24-hour urine protein/creatinine ratios developed in dogs with membranous glomerulonephritis. Although hypoalbuminemia and hypercholesterolemia were common (49%), the formation of edema or ascites was not (15%) and, therefore, few dogs had all of the classic features of the nephrotic syndrome. Few dogs suffered thromboembolic complications. Antinuclear antibody titers developed in 11 dogs, the highest titers developing in dogs with polyarthritis and systemic lupus erythematosis. Cellulose acetate electrophoresis detected alpha 2 and beta 1 globulin spikes in most dogs (87%). Results of renal immunofluorescence testing were positive in 36 dogs, using polyvalent antisera for immunoglobulins (Ig)G, IgA, IgM, and/or antisera for complement factor C3. When monovalent antisera for IgG, IgA, and IgM, and fibrinogen were used, immunofluorescence was not observed as often. The major fluorescent pattern was discrete multifocal segmental granular glomerular fluorescence, consistent with immune-complex deposition. Two dogs had linear glomerular staining patterns; however, antibodies directed against normal glomerular basement membrane were not found via elution studies. A high prevalence of glucocorticoid excess (treatment with glucocorticoids and spontaneous hyperadrenocorticism) (34%), chronic inflammatory skin disease (27%), neoplasia (17%), polyarthritis (12%), and systemic lupus erythematosis (7%) were observed as clinical problems concurrent with glomerulonephritis. In 5 dogs, treatment of glomerulonephritis with prednisolone (0.5 to 1.1 mg/kg) did not result in beneficial effects and in fact appeared to be detrimental, leading to azotemia and worsening proteinuria and physical condition in some of the dogs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunopathological aspects of canine renal disease

It is now becoming clear that the development of immunity against an infectious agent is not always beneficial to the host and may sometimes be instrumental in exacerbating the disease process. Thus, it is important to define the nature of the immunological processes which undoubtedly play an important role in some of the important renal diseases of the dog.
Deposition of immune complexes in the glomeruli stimulates a range of morphological types of glomerulonephritis. The persistence of leptospiral antigen, alone or complexed with locally produced antibody, in the renal interstitium appears to be responsible for the marked cellular response in acute leptospiral nephritis. In chronic forms of diffuse renal disease, glomerular immune complexes have been detected in chronic glomerulonephritis but not with certainty in chronic interstitial nephritis.     

Renal pathology in working dogs in the South African National Defence Force

Urine analysis, serum biochemical profile and a cortical wedge biopsy for histopathological examination was performed on 42 South African National Defence Force (SANDF) dogs from around the country. The only significant finding on urine analysis and serum biochemistry was a relatively large number (16/42) of dogs with elevated serum inorganic phosphate levels. Histopathology revealed that only 9 of the animals had normal kidneys reflected in the wedge biopsy material, with over 50% of them showing signs of glomerular pathology (primarily mesangioproliferative glomerulonephritis). Other conditions detected histopathologically were haemosiderosis (47% of animals), focal nephrosis (2.4%), membranoproliferative glomerulonephritis (2.4%), focal interstitial nephritis (4.7%) and acute tubular nephrosis (4.7%). The lesions observed were of limited distribution and extent; this histopathological finding may account for the absence of significant abnormalities on urine analysis or serum biochemistry profiles. It appears from these results that a large percentage of the SANDF population would be expected to have mild renal lesions, but that these lesions are not severe enough to lead to clinical signs. The findings of this study are similar to those of randomly selected populations of non-military dogs performed in other areas of the world, which also demonstrated an unexpectedly high incidence of histopathological renal pathology in dogs considered healthy. These lesions may well, however, play a role in later life, and it is recommended that military veterinarians maintain an index of suspicion for renal disease, particularly glomerular disease. The aetiology of the histopathological lesions is unknown.