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.     

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.     

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.     

Histopathological retrospective study of canine renal disease in Korea, 2003~2008

Renal disease includes conditions affecting the glomeruli, tubules, interstitium, pelvis, and vasculature. Diseases of the kidney include glomerular diseases, diseases of the tubules and interstitium, diseases of renal pelvis, and developmental abnormalities. Renal tissue samples (n = 70) submitted to the Department of Veterinary Pathology of Konkuk University from 2003 to 2008 were included in this study. Tissue histopathology was performed using light microscopy with hematoxylin and eosin stains. Masson''s trichrome, Congo Red, and Warthin starry silver staining were applied in several individual cases. Glomerular diseases (22.9%), tubulointerstitial diseases (8.6%), neoplastic diseases (8.6%), conditions secondary to urinary obstruction (24.3%), and other diseases (35.7%) were identified. Glomerulonephritis (GN) cases were classified as acute proliferative GN (5.7%), membranous GN (4.3%), membranoproliferative GN (4.3%), focal segmental GN (2.9%), and other GN (4.2%). The proportion of canine GN cases presently identified was not as high as the proportions identified in human studies. Conversely, urinary obstruction and end-stage renal disease cases were relatively higher in dogs than in human populations.     

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.     

Supplementation of heterologous complement induces anti-Thy-1.1 nephritis in the Mongolian gerbil (Meriones unguiculatus)

Anti-Thy-1.1 nephritis in the rat is a popular experimental model for mesangial proliferative glomerulonephritis (GN). This model is characterized by direct binding of anti-Thy-1.1 antibody with Thy-1.1 antigen expressed on mesangial cells (MCs) of glomeruli in the rat. A single injection of anti-rat thymocyte serum (ARTS) results in GN with proteinuria and extensive mesangiolysis. Development of mesangiolysis and proteinuria are complement-dependent. We previously demonstrated Thy-1.1 antigen, similar to the rat, in thymocytes, brain cells and MCs of the kidney in the Mongolian gerbil (MG). In this study, we attempted to develop a MG nephritis model, but an injection of ARTS did not induce GN. An additional injection of guinea pig serum as a complement after ARTS injection resulted in anti-Thy-1.1 nephritis in MG. Degeneration of MCs and neutrophil infiltration were observed 1 hr after GP serum injection. Mesangiolysis and fibrin exudation occurred 12 hr after the injection and MC proliferation was apparent 7 days after the injection. In the complement-dependent hemolytic test, MG serum could not hemolyze sheep erythrocytes. These results suggested low activity, or depletion of some factors, in complements of MG serum.     

Age-related renal, hematologic, and hemostatic abnormalities in FH/Wjd rats

This longitudinal study compared the renal morphologic changes and hemostatic defects of FH/Wjd rats at different ages. A second aim was to determine whether the bleeding tendency becomes intensified in older animals by the concomitant renal disease. Results indicated that reduced capacity for platelet 14C-serotonin release (P less than 0.01) was found for each age group studied in comparison with Wistar controls. The nephropathy of old FH/Wjd male rats was more severe than that in either FH/Wjd females or age-matched Wistars of both sexes. The mesangial lesions showed abundant deposits of factor VIII-related antigen, fibronectin, and immunoglobulins, but not C3, along with tightly packed or loose electron-dense material. Polyethylene glycol precipitation and platelet aggregation tests detected small amounts of circulating immune complex-like material. Old FH/Wjd rats did not develop edema, and the glomerular filtration rate remained normal despite the persistent proteinuria, hematuria, and arterial hypertension characteristic of this strain. Our data indicated that the congenital platelet dysfunction does not become more severe in older animals and that the nephropathy seems unrelated, does not appear to be mediated by immune complexes, and, in contrast to the focal segmental glomerulosclerosis of persons, the lesions progress without a parallel impairment of renal function.     

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.     

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.     

Age-related changes in calretinin-immunoreactive periglomerular cells in the rat main olfactory bulb

The changes of calretinin (CR)-immunoreactive periglomerular cells in the glomerular layer of the main olfactory bulb (MOB) were investigated in rats differing ages from postnatal month 1 (PM 1) to PM 24. The number of cresyl violet-positive periglomerular cells was similar between PM 1 and PM 12, but they decreased slightly in the PM 24 group. The size of CR-immunoreactive periglomerular cells in the glomerular layer increased with age, while their numbers did not change significantly in the PM 6-PM 24 groups. In the PM 24 group, numbers of CR-positive periglomerular cell bodies and their processes decreased, while the size of CR-positive cell bodies in the glomeruli was larger than that of the previous groups. These results suggest that CR-immunoreactive periglomerular cells in the rat MOB are well-developed in the PM 6 group, and that periglomerular cells in the PM 24 group show poor CR-immunoreactivity compared to those in the PM 6 group.     

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.     

Glomerular Ultrastructural Findings Similar to Hereditary Nephritis in 4 English Cocker Spaniels

Renal disease affecting 3 male and 1 female English Cocker Spaniels was studied. Clinical features of the disease included proteinuria and progressive deterioration of renal function. Dogs were 11 to 27 months old when euthanized because of severe chronic renal failure. Grossly, the renal cortices were thin. Light microscopic evaluation revealed diffuse glomerular disease characterized by mesangial thickening, glomerular fibrosis, periglomerular fibrosis, and glomerular obsolescence. Based on these clinical and pathologic features, familial nephropathy of English Cocker Spaniels was suspected despite the fact that the individual dogs were not closely related. On transmission electron microscopy, a distinctive ultrastructural lesion was observed in the glomerular basement membranes (GBM) of all dogs. The GBM exhibited extensive thickening, multilaminar splitting, and fragmentation. Electron dense deposits, suggestive of immunocomplex glomerular disease, were notably absent. A similar ultrastructural GBM lesion is found in human beings and Samoyeds with hereditary nephritis, diseases caused by mutations in the type IV collagen genes. Familial nephropathy in English Cocker Spaniels may be a form of hereditary nephritis caused by a mutation in one of the collagen IV genes.     

Evaluation of the effects of inhibition of angiotensin converting enzyme with enalapril in dogs with induced chronic renal insufficiency

OBJECTIVE: To determine whether the angiotensin converting enzyme inhibitor enalapril would lower systemic arterial and glomerular capillary pressure and reduce the magnitude of renal injury in a canine model of renal insufficiency. ANIMALS: 18 adult dogs that had renal mass reduced by partial nephrectomy. PROCEDURE: After surgical reduction of renal mass and baseline measurements, dogs in 2 equal groups received either placebo (group 1) or enalapril (0.5 mg/kg, PO, q 12 h; group 2) for 6 months. RESULTS: Values for systemic mean arterial blood pressure determined by indirect and direct measurement after 3 and 6 months of treatment, respectively, were significantly lower in group 2 than in group 1. During treatment, monthly urine protein-to-creatinine ratios were consistently lower in group 2 than in group 1, although values were significantly different only at 3 months. At 6 months, significant reduction in glomerular capillary pressure in group 2 was detected, compared with group 1, but glomerular filtration rate in group 2 was not compromised. Glomerular hypertrophy, assessed by measurement of planar surface area of glomeruli, was similar in both groups. Glomerular and tubulointerstitial lesions were significantly less in group 2, compared with group 1. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that inhibition of angiotensin converting enzyme was effective in modulating progressive renal injury, which was associated with reduction of glomerular and systemic hypertension and proteinuria but not glomerular hypertrophy. Inhibition of angiotensin converting enzyme may be effective for modulating progression of renal disease in dogs.     

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

Twelve Beagles were inoculated with concanavalin A, and after a mean ninefold increase in antibody titer, 1 mg of concanavalin A was infused into each renal artery of each dog to induce in situ immune complex glomerulonephritis. Starting 4 weeks after renal arterial infusion, 6 dogs were treated orally 3 times daily with 30 mg of 3-methyl-2 (3 pyridyl)-1-indolectanoic acid (CGS 12970)/kg of body weight, a thromboxane synthetase inhibitor, and 6 dogs (control group) received a gelatin capsule 3 times daily. Endogenous creatinine clearance and 24-hour urinary excretion of protein and thromboxane B2 were determined for each dog prior to renal arterial infusion, at the initiation of treatment and at 2, 4, 6, and 8 weeks after initiation of treatment. In addition, methyoxy-3H inulin clearance was determined at initiation of treatment and 4 and 8 weeks later. Renal specimens were examined histologically at the initiation of treatment and 4 and 8 weeks later. Glomerular mononuclear profiles/microns 3 were determined from at least 10 equatorially sectioned glomeruli from each dog. Paired t tests were used to compare mean values at the various time points to the respective mean baseline value and 2-sample t tests were used to evaluate differences between treatment groups. At the start of treatment (4 weeks after renal arterial infusion of concanavalin A), histologic evaluation of renal specimens revealed glomerular epithelial crescent formation, mononuclear cell proliferation, and infiltration of neutrophils. Mononuclear cell profiles and urinary excretion of protein and thromboxane B2 were significantly increased, but endogenous creatinine clearance values were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Collagenofibrotic glomerulonephropathy in a cynomolgus macaque (Macaca fascicularis)

Collagenofibrotic glomerulonephropathy (CFGN) is characterized by the deposition of type III collagen within the mesangial matrix and the absence of mesangial cell proliferation. A case of CFGN in a 2.7-year-old female cynomolgus macaque was investigated in the present study. Clinically, the animal was shown to have severe systemic edema along with hypoproteinemia. At necropsy, the kidneys were swollen and pale. The glomerular lesions were characterized by massive diffuse and global accumulation of fibrous materials in the mesangial areas. Neither mesangial cell proliferation nor changes in other organs were found. The fibrous materials were confirmed by the results of immunohistochemical and electron microscopic findings to consist mainly of randomly arranged, curve-shaped, twisted, and entwined type III collagen. This is the first case report of CFGN in nonhuman primates to date.     

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.     

Pathogenicity of an Indian isolate of bovine viral diarrhea virus 1b in experimentally infected calves

The aim of this study was to determine the pathogenicity of an Indian bovine viral diarrhea virus (BVDV) 1b isolate in 7-9-months-old male calves. Infected (four) and control (two) calves were bled at three days interval for hematological, virological and serological studies until day 27. All infected calves developed respiratory illness, biphasic pyrexia, mild diarrhea, leucopenia and mild thrombocytopenia. Viraemia was demonstrated between 3 and 15dpi and the infected calves seroconverted by 15dpi. Prominent kidney lesions were endothelial cell swelling, proliferation of mesangial cells and podocytes leading to glomerular space obliteration. Degeneration and desquamation of cells lining seminiferous tubules were observed in two infected calves. Consolidation of lungs with interstitial pneumonia, mild gastroenteritis and systemic spread were also evident. It was concluded that Indian BVDV isolate induced moderate clinical disease in calves and glomerulonephritis resulting from acute BVDV infection was observed for the first time.     

Effects of Glucocorticoid Therapy on Urine Protein-to-Creatinine Ratios and Renal Morphology in Dogs

Glomerulonephritis has been associated with exogenous glucocorticoid administration and spontaneous hyperadrenocorticism in the dog. The purpose of this study was to determine the effects of long-term glucocorticoid therapy on urine protein:creatinine ratios (UP/Cs) and renal morphology. Nine young-adult male dogs were determined to be healthy and have normal renal function as assessed by physical examination, CBC, serum biochemistry analysis, Knott's test for Dirofilaria immitis , urinaly-sis, urine culture, urine protein electrophoresis, endogenous creatinine clearance, 24-hour urinary protein excretion, and UP/C. Prednisone was administered to each dog at a dosage of 2.2 mg/kg PO bid for 42 days. Urinalysis and UP/C were performed on days 0, 7, 14, 21, 28, and 42 of treatment. Mean UP/C on day 0 was 0.29 ± 0.10. Mean UP/C increased progressively to a maximum of 1.27 ± 1.02 on day 28. Mean UP/C on day 42 decreased slightly (0.92 ± 0.56) but remained significantly increased above baseline.
The most consistent renal light microscopic finding on necropsy examination was generalized hypercellular glomerular tufts, suggestive of mesangial cell proliferation. Four dogs also had occasional adhesions of glomerular tufts to Bowman's capsule, accompanied by thickening of the capsule. Direct immunofluorescence for immunoglobulin deposition was negative in all dogs. Electron microscopy, evaluated in 7 dogs, was characterized by occasional mild segmental thickening of basement membranes, fusion of visceral cell foot processes, and glomerular adhesions. The results of this study indicate that long-term administration of glucocorticoids results in significant proteinuria and glomerular changes in the dog.     

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.