MicroRNA-126 in dogs with immune complex-mediated glomerulonephritis.

BACKGROUND: Most proteinuric dogs with naturally occurring chronic kidney disease have amyloidosis (AMYL), glomerulosclerosis (GS), or immune complex-mediated glomerulonephritis (ICGN), each with different treatment and prognosis. A noninvasive and disease-specific biomarker is lacking. HYPOTHESIS: We hypothesized that the expression pattern of biofluid microRNA (miRNAs and miRs) would correlate with disease progression and categorization. ANIMALS: Archived serum and urine samples from 18 dogs with glomerular disease and 6 clinically healthy dogs; archived urine samples from 49 dogs with glomerular disease and 13 clinically healthy dogs. METHODS: Retrospective study. Archived biofluid samples from adult dogs with biopsy-confirmed glomerular disease submitted to the International Veterinary Renal Pathology Service between 2008 and 2016 were selected. Serum and urinary miRNAs were isolated and profiled using RNA sequencing. Urinary miR-126, miR-21, miR-182, and miR-486 were quantified using quantitative reverse transcription PCR. RESULTS: When comparing more advanced disease with earlier disease, no serum miRNAs were differentially expressed, but urinary miR-21 and miR-182 were 1.63 (95% CI: .86-3.1) and 1.45 (95% CI: .82-2.6) times higher in azotemic dogs, respectively (adjusted P < .05) and weakly correlated with tubulointerstitial fibrosis (miR-21: r = .32, P = .03; miR-182: r = .28, P = .05). Expression of urinary miR-126 was 10.5 (95% CI: 4.1-26.7), 28.9 (95% CI: 10.5-79.8), and 126.2 (95% CI: 44.7-356.3) times higher in dogs with ICGN compared with dogs with GS, AMYL, and healthy controls, respectively (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The miR-126 could help identify dogs that might benefit from immunosuppressive therapy in the absence of a biopsy. MiR-21 and miR-182 are potential markers of disease severity and fibrosis.

Concomitant Congenital Diaphagmatic Hernia (CDH) and bilateral bacterial glomerulonephritis in a pet chinchilla (Chinchilla lanigera).

BACKGROUND: The domestic chinchilla has been descended from Chinchilla lanigera (long-tailed Chinchilla) or Chinchilla chinchilla (short-tailed Chinchilla). Both species of chinchilla are currently listed as endangered by the IUCN Red List of Threatened Species. Over the past 20 years, they have spread as pets and overall knowledge about their care is improving. The present case report describes a congenital diaphragmatic hernia in a Chinchilla lanigera. CASE PRESENTATION: A 1-year-old, 420 g female chinchilla (Chinchilla lanigera) was presented for clinical examination due to 2 days haematuria episodes and anorexia. A complete haematological analysis was performed, showing a moderate neutrophilia and severe renal involvement. X-rays showed severe intestinal meteorism affecting mostly the cecum, and a soft tissue density mass with translucent areas located in the caudal thorax, making it hard to distinguish the cardiac silhouette. A barium swallow (barium sulfate) was performed and after 20 min, radiograms were performed again, showing part of the stomach dislocated in thorax. Ultrasound was also carried out, confirming the partial stomach herniation into the thoracic cavity and a severe nephropathy. The patient was euthanized according to the owner's wish and a complete necropsy was performed. The diagnosis was congenital diaphragmatic hernia concomitant to a severe bilateral bacterial glomerulonephritis. DISCUSSION AND CONCLUSIONS: Diaphragmatic hernias can be either congenital or acquired. About CDHs in pet chinchillas, literature is still lacking. In this patient there was no history of previous traumas. No scar tissue or thickening involved margins of the pathological diaphragm window at the necropsy, supporting the hypothesis of a congenital defect. Glomerulonephritis most often results from immune-mediated mechanisms, generally after the deposition of soluble immune complexes within the glomeruli. This mechanism is favoured by a prolonged antigenemia that could occur during specific viral infections, chronic bacterial infections, chronic parasitism, autoimmune diseases and neoplasia. Few cases of nephritis are described in chinchillas (Chinchilla lanigera), mostly related to bacterial sepsis or less commonly involving fungi. The evidence of bacterial aggregates in kidneys at the histopathology, confirmed the infective aetiology. No relationship between the diaphragmatic hernia and glomerulonephritis was found in this report.

Glomerulonephritis after contact with a horse. / Glomerulonefritt etter kontakt med hest.

BACKGROUND: Zoonoses are important to consider when humans become ill after being in contact with animals. In such cases thorough patient history is crucial, especially when infections have an unclear cause. We present a patient with infection-associated glomerulonephritis, where a horse was the probable source of infection. CASE PRESENTATION: A young woman was admitted to the district general hospital in Vestfold, Norway, with infection and acute kidney failure. Renal biopsy suggested glomerulonephritis, and nasopharyngeal culture taken at admission detected Streptococcus equi. It emerged that the patient had daily contact with horses. INTERPRETATION: As Streptococcus equi is not part of normal human flora and the clinical signs were compatible with infection-associated glomerulonephritis, it was considered a probable causal link between the microbial finding and diagnosis. The source of infection was one of the horses.

Occurrence, management and outcome of immune-complex glomerulonephritis in dogs with suspected glomerulopathy in the UK.

OBJECTIVES: To determine the proportion of dogs diagnosed with immune-complex glomerulonephritis in a large cohort of UK dogs with clinical suspicion of glomerular disease in which renal histopathology, including routine light microscopy, transmission electron microscopy and immunofluorescence, had been performed. The second objective was to describe treatment and long-term clinical outcome of dogs diagnosed with immune-complex glomerulonephritis. MATERIALS AND METHODS: Sixty-two UK dogs that underwent renal biopsies for investigation of suspected glomerulopathy (urine protein-to-creatinine ratio persistently >0.5) were included in this retrospective multicentre study. Signalment, clinico-pathological abnormalities, histopathological diagnosis, treatment following diagnosis and survival were recorded. RESULTS: Seventeen (27%) of the dogs with suspected glomerular disease were diagnosed with immune-complex glomerulonephritis and nine (53%) of these were still alive at the study end point, with a median follow-up of 366 days (range 52 to 1299). Six dogs diagnosed with immune-complex glomerulonephritis were treated with mycophenolate. Four received mycophenolate alone for immunosuppression and two received mycophenolate and chlorambucil; all these six dogs were alive at data collection [median follow-up time 712.5 days (range 73 to 1299)]. Seven dogs diagnosed with immune-complex glomerulonephritis did not receive immunosuppressive treatment; only one of these dogs was alive at study end point [median survival time 302 days (range 52 to 723)]. CLINICAL SIGNIFICANCE: Immune-complex glomerulonephritis may be less common in the UK than previously reported in North America and mainland Europe, reducing the likelihood of treatment modification following renal biopsy. Mycophenolate was the most commonly used immunosuppressant for cases of immune-complex glomerulonephritis.

Immune-complex glomerulonephritis in cats: a retrospective study based on clinico-pathological data, histopathology and ultrastructural features.

BACKGROUND: Chronic kidney disease (CKD) has typically a non-immune mediated origin in cats and immune-complex glomerulonephritis (ICGN) is scarcely described. Aims of this study were to characterize ICGN by light and electron microscopy and identify associations with clinico-pathological findings. In addition, comparisons between cats with ICGN and non immune-complex glomerulonephritis (non-ICGN) were performed. Renal samples examined between 2010 and 2019 were considered if both light and electron microscopy were performed. Signalment, feline immunodeficiency virus (FIV) and leukemia virus (FeLV) status, serum creatinine concentration, urine protein-to-creatinine (UPC) ratio, systolic blood pressure (SBP) and International Renal Interest Society (IRIS) stage were retrieved and used for comparisons. RESULTS: Sixty-eight client-owned cats were included. Thirty-seven cats (54.4%) had ICGN and 31 (45.6%) non-ICGN. Eighteen (48.6%) with ICGN had membranous glomerulonephropathy (MGN), 14 (37.8%) membranoproliferative glomerulonephritis (MPGN), and 5 (13.5%) mesangioproliferative glomerulonephritis (MeGN). Clinico-pathological data were not associated with any type of ICGN. Among cats with non-ICGN, 11 (35.5%) had end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal mesangiosclerosis, 2 (6.5%) glomerular atrophy, 2 (6.5%) renal dysplasia and 1 (3.1%) amyloidosis. Eight (25.8%) cats with non-ICGN had chronic interstitial nephritis (CIN) grade 1, 13 (41.9%) grade 2 and 10 (32.3%) grade 3; creatinine and UPC ratio increased with CIN grades (p = 0.001, p < 0.001). Cats with ICGN were more frequently FIV or FeLV-infected (OR:11.4; 95%CI:1.4-94.4; p = 0.024), had higher UPC ratio (OR:6.8; 95%CI:2.5-18.2; p < 0.001) and were younger (OR:0.9; 95%CI:0.7-1.0; p = 0.042) than cats with non-ICGN. CONCLUSIONS: MGN and MPGN were the most common morphological diagnoses of ICGN in cats. Unfortunately, none of the investigated findings differentiated ICGN morphological diagnoses. Serum creatinine concentration and UPC ratio were directly associated with grades of CIN (p = 0.001 and p < 0.001, respectively), confirming previous literature. More ICGN than non-ICGN was observed in cats with retroviral infections, younger cats and higher UPC ratio.

Biomarkers and renal arterial resistive index in dogs naturally infected with Leishmania infantum.

Canine visceral leishmaniasis frequently causes glomerulonephritis and tubulointerstitial nephritis, nephropathies for which diagnosis has been limited by the low sensitivity of traditional tests. The aim of this study was to evaluate serum cystatin C and urinary gamma-glutamyltransferase (uGGT) levels and the urinary GGT/urinary creatinine ratio (uGGT/uCR) and to measure the renal arterial resistive index (RARI) in dogs with leishmaniasis with varying degrees of renal injury based on the urine protein: creatinine ratio (UP/C) and serum creatinine (SCr) level. We tested 59 untreated adult dogs of both sexes and undefined breeds naturally infected with Leishmania infantum. The dogs were grouped into four groups based on UP/C and SCr level: group 1 (n = 15), dogs with SCr levels < 1.4 mg/dL and UP/C < 0.5; group 2 (n = 13), dogs with SCr levels < 1.4 mg/dL and UP/C of 0.5-1.0; group 3 (n = 16), dogs with SCr levels < 1.4 and UP/C > 1.0; and group 4 (n = 15), dogs with SCr levels > 1.4. A fifth group of healthy dogs (n = 10) was the control. uGGT concentrations and uGGT/uCR were higher in dogs with proteinuria and SCr < 1.4 mg/dL, whereas the serum cystatin C concentrations and RARI were higher only in dogs with SCr levels > 1.4. In conclusion, uGGT and uGGT/uCR may be useful tools for early detection and assessment of renal lesions associated with leishmaniasis; however, cystatin C is useful for monitoring the progression of kidney disease when measured sequentially.

Comparison of immunohistochemistry and immunofluorescence techniques using anti-lambda light chain antibodies for identification of immune complex deposits in canine renal biopsies.

Comprehensive renal biopsy evaluation of canine glomerular disease uses immunofluorescence (IF) labeling of fresh frozen tissue to detect immune complexes that are confirmed with transmission electron microscopy. This methodology requires the veterinarian to harvest additional tissue samples, whereas sections for immunohistochemistry (IHC) could be performed on paraffin sections. If adequate IHC labeling of formalin-fixed, paraffin-embedded tissue was possible, the additional tissue samples would be unnecessary. We compared the specificity and sensitivity of IHC to IF for diagnosis of immune complex-mediated glomerulonephritis (ICGN). Commercial anti-canine IHC and IF antibodies targeting the lambda light chain component of immunoglobulins were evaluated, using previously diagnosed cases of ICGN and cases without immune complexes (non-ICGN). Because the pattern of IF labeling is crucial for accurate interpretation, sections were evaluated by a trained nephropathologist and a novice to assess the impact of experience in the diagnosis of ICGN. Unfortunately, our attempts to develop an IHC protocol that could improve the workflow for clinicians and laboratory personnel were unsuccessful; the IHC protocol did not demonstrate staining patterns that could be detected reliably by either evaluator. Moreover, the IHC antibody demonstrated abundant nonspecific staining in non-ICGN cases, and 60% of true ICGN cases were misdiagnosed as non-ICGN. We did not achieve a reliable IHC protocol for the anti-lambda light chain antibody and, therefore, IF for lambda light chain remains the method of choice for ICGN detection.

Potential role of lncRNAs in contributing to pathogenesis of chronic glomerulonephritis based on microarray data.

BACKGROUND: Chronic glomerulonephritis (CGN) is the most common form of primary glomerular disease with unclear molecular mechanisms, which related to immune-mediated inflammatory diseases. Our study intended to identify potential long non-coding RNAs (lncRNAs) and genes, and to determine the potential molecular mechanisms of CGN pathogenesis. METHODS: The microarray of GSE64265 and GSE46295 were downloaded from the Gene Expression Omnibus database, GSE64265 including 3 rats control kidney tissues and 5 rats model kidney tissues, GSE46295 including 3 rats control kidney tissues and 3 rats model kidney tissues, which was on the basis of GPL1355 platform. Identification of differentially expressed lncRNAs and mRNAs were performed between the 2 groups. Gene ontology (GO) and pathway enrichment analyses were performed to analyze the biological functions and pathways for the differentially expressed mRNAs. LncRNA-mRNA weighted co-expression network was constructed using the WGCNA package to analyses for the genes in the modules. The protein-protein interaction (PPI) network was visualized. RESULTS: A total of 40 significantly up-regulated and 24 down-regulated lncRNAs, 653 up-regulated and 128 down-regulated mRNAs were identified. Additionally, Cdk1, with the highest connectivity degree in PPI network, was noteworthy enriched in cell cycle. Seven lncRNAs: NONRATT026650, LOC102547664, NONRATT77021989, NONRATT012453, LOC102551856, LOC102553536 and NONRATT7047175 were observed in the modules of lncRNA-mRNA weighted co-expression network. CONCLUSIONS: LncRNAs NONRATT026650, LOC102547664, NONRATT77021989, NONRATT012453, LOC102551856, LOC102553536 and NONRATT7047175 were differentially expressed and might play important roles in the development of CGN. Key genes, such as Cd44, Rftn1, Runx1, may be crucial biomarkers for CGN.

Paraffin immunofluorescence for detection of immune complexes in renal biopsies: an efficient salvage technique for diagnosis of glomerulonephritis in dogs.

BACKGROUND: Renal biopsy is an essential tool for the diagnosis of proteinuric kidney diseases in dogs, and evaluation of immune complexes (IC) by immunofluorescence (IF) of frozen sections (IF-F) is required for the diagnosis of IC-mediated glomerulonephritis (ICGN). However, the use of frozen sections from renal biopsies can have limitations. The aim of this study was to develop a reliable IF method using formalin-fixed and paraffin-embedded (FFPE) sections to detect ICs in dog ICGN. METHODS: Renal biopsy specimens were obtained from dogs with protein-losing nephropathies. FFPE sections were prepared, and eight antigen retrieval pretreatment protocols were performed: digestion with trypsin, microwave (MW) heating in citrate buffer (MW-CB; pH 6.0), MW heating in Tris-EDTA buffer (MW-TEB; pH 9.0), as well as combinations of the above, and a non-treated control. RESULTS: A combination of trypsin for 30 min (Try-30) and MW-TEB; pH 9.0 was the most effective antigen retrieval pretreatment, with clear positive signals for IgG, IgA, IgM, and C3 detected by IF-FFPE. Granular signals, an important diagnostic indicator of ICGN, were clearly observed by both IF-F and IF-FFPE after combined pretreatment with Try-30 and MW-TEB, and IgG, IgA, IgM, and C3 signals were almost completely matched in all samples by IF-F and IF-FFPE. CONCLUSION: IF-FFPE with Try-30 and MW-TEB pretreatment is a valuable technique for the diagnosis of renal diseases in dogs. This method could be an efficient tool when standard IF-F cannot be used, or does not provide useful results due to lack of glomeruli in the specimens for IF-F.

European Veterinary Renal Pathology Service: A Survey Over a 7-Year Period (2008-2015).

BACKGROUND: The European Veterinary Renal Pathology Service (EVRPS) is the first Web-based registry for canine renal biopsy specimens in Europe. HYPOTHESIS/OBJECTIVES: The aim was to verify whether differences exist between the clinical and laboratory presentation of dogs with nephropathy according to renal pathological findings, as defined by light and electron microscopy of renal biopsy specimens submitted to EVRPS. ANIMALS: Renal biopsy specimens of dogs were collected from the archive of the service (n = 254). Cases were included if both light and electron microscopy were available (n = 162). METHODS: Renal biopsy specimens were classified based on the morphological diagnoses. Thereafter, they were grouped into 3 disease categories, including immune-complex-mediated glomerulonephritis (ICGN), non-immune-complex-mediated GN (non-ICGN), and renal lesions not otherwise specified (RL-NOS). Differences among morphological diagnoses and among disease categories were investigated for clinical and laboratory variables. RESULTS: Serum albumin concentration was lower in dogs with ICGN than in those with non-ICGN (P = 0.006) or RL-NOS (P = 0.000), and the urine protein-to-creatinine ratio (UPC) was significantly higher in ICGN than in the other 2 disease categories. Regarding morphological diagnoses, albumin was significantly lower in amyloidosis (AMY) and membranous (MGN), membranoproliferative (MPGN) or mixed glomerulonephritis (MixGN) than in minimal change disease, primary (FSGS I) or secondary (FSGS II) focal and segmental glomerulosclerosis and juvenile nephropathies (JN). The UPC was higher in MPGN than in FSGS I and FSGS II. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with ICGN, in particular MPGN, had higher protein loss than those with non-ICGN or RL-NOS, leading to more severe hypoalbuminemia. Clinical and laboratory differentiation among dogs with the different morphological diagnoses and among dogs with different disease categories was difficult due to overlapping results.

World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed.

Clinical and histopathological features resembling those of human focal segmental glomerulosclerosis in a cat with nonimmune-mediated glomerulonephropathy.

BACKGROUND: Nonimmune-mediated glomerulonephropathies are rarely reported in domestic animals with the exception of amyloidosis. Here we describe the pathological features and clinical course of a feline with protein-losing nonimmune-mediated glomerulonephropathy characterized by segmental glomerulosclerosis and severe podocyte injury. CASE PRESENTATION: A castrated male Japanese domestic cat aged 3 years and 8 months had hypertension, persistent proteinuria, and azotemia. Microscopic examination of a renal biopsy revealed many glomeruli with adhesion to the Bowman's capsule and segmental sclerosis. The most characteristic ultrastructural glomerular feature was severe podocyte foot process effacement. No electron-dense deposits were observed. Immunofluorescence revealed no immune deposits, but abnormal expression of nephrin and podocin was detected in the glomeruli. These findings resemble those of human focal segmental glomerulosclerosis. The cat temporarily responded to treatment with angiotensin-converting enzyme inhibitors and prednisolone administration but died of progressive renal failure 32 months after biopsy. CONCLUSIONS: The cat was diagnosed with nonimmune mediated glomerulonephropathy because of the absence of immune deposits and severe podocyte injury. To our knowledge, this is the first report of nonimmune-mediated glomerulonephropathy in a cat resembling human focal segmental glomerulosclerosis.

Glomerulonephritis in a ferret with feline coronavirus infection.

A male domestic ferret (Mustela putorius furo), which was purchased from outside of Japan at 13 weeks of age, was euthanized at 18 months of age because of poor health. At autopsy, the liver, spleen, and mesenteric lymph node were enlarged, and white foci were observed on the outer surface of the liver. The outer surface of the mesenteric lymph node was dark red. Histologically, granulomas were observed in the liver, spleen, bone marrow, and lymph nodes, composed mainly of aggregated epithelioid macrophages, some of which were positive to an anti-feline coronavirus (FCoV; Alphacoronavirus 1) antibody in immunohistochemistry. Mesangioproliferative glomerulonephritis was observed, and periodic acid-Schiff-positive deposits were observed along glomerular capillary walls. These deposits stained pale red with periodic acid-methenamine silver stain and red with Masson trichrome stain, and were also observed in the mesangial matrix. In affected glomeruli, glomerular capillary walls and mesangial areas were positive for anti-ferret immunoglobulin G. By electron microscopy, subepithelial and mesangial electron-dense deposits were observed consistent with immune complex deposition. The deposition of immune complexes may have been associated with FCoV infection.

Congenital Extrahepatic Abdominal Arteriovenous Fistula and Apparent Patent Ductus Venosus in a Dog.

A 3 mo old male German shepherd dog presented with a 2 wk history of diarrhea with possible melena followed by inappetence and progressive abdominal distension. Clinical findings, serum biochemical analysis, and abdominal ultrasound were highly suggestive of an extrahepatic abdominal arteriovenous fistula and concurrent patent ductus venosus, which were confirmed during an abdominal exploratory surgery. Renal biopsies taken at the time of surgery confirmed a chronic glomerulopathy. The dog made a good initial recovery from the procedure but was euthanatized 6 wk postoperatively for medically unresponsive renal disease.

Acute and Chronic Erysipelothrix rhusiopathiae Infection in Lambs.

Polyarthritis caused by Erysipelothrix rhusiopathiae is a relatively common infection in lambs characterized by low mortality and high morbidity. E. rhusiopathiae is a ubiquitous Gram-positive bacterium that is both a commensal and a pathogen of vertebrates. The disease was studied during an outbreak in a Norwegian Spæl sheep flock. In the acute phase, 48 of 230 (20%) lambs developed clinical signs and 4 died (1.7%). One acute case was necropsied and E. rhusiopathiae was cultured from all major organs investigated and from joints. There was a fibrinous polyarthritis, increased presence of monocytes in vessels, and necrosis of Purkinje cells. Sixteen of the diseased animals (33%) developed a chronic polyarthritis. Eight of these lambs were necropsied; all had lesions in major limb joints, and 3 of 8 also had lesions in the atlanto-occipital joint. At this stage, E. rhusiopathiae was cultured only from the joints in 7 of 8 (87.5%) lambs, but by real-time polymerase chain reaction, we showed persistence of the bacterium in several organs. Pulsed-field gel electrophoresis typing of the bacterial isolates indicated that the same strain caused the acute and chronic disease. Five of 6 (83%) chronically affected animals had amyloidosis of the spleen, and 6 of 8 (75%) had amyloidosis of the liver. All chronically affected animals had a glomerulonephritis, and 6 of 8 (75%) had sparse degeneration in the brain. Ceruloplasmin and haptoglobin were significantly increased in the chronically diseased lambs. These results show that chronic ovine erysipelas is not restricted to joints but is a multisystemic disease.

Aspectos histopatológicos das lesões renais em gatos experimentalmente infectados pelo vírus da imunodeficiência felina / Histopathological aspects of renal lesions in cats experimentally infected with feline immunodeficiency virus

A infecção pelo vírus da imunodeficiência felina (FIV) em gatos domésticos é caracterizada por distúrbios imunológicos, que geralmente se manifestam tardiamente na doença. Semelhante à infecção pelo vírus da imunodeficiência humana (HIV) em humanos, a infecção pelo FIV geralmente está associada a infecções oportunistas e ao desenvolvimento progressivo de nefropatia. Portanto, o objetivo do presente estudo foi avaliar as alterações histopatológicas em rins de 10 gatos experimentalmente infectados pelo FIV submetidos a eutanásia 60 meses após a inoculação viral. Nos rins de 100% dos gatos infectados pelo FIV foram visualizadas lesões glomerulares e tubulointersticiais. As lesões glomerulares eram caracterizadas principalmente por espessamento global ou segmentar da membrana basal glomerular (glomerulonefrite membranosa). Glomeruloesclerose e, em dois casos, proliferação de células epiteliais intraglomerulares (crescente glomerular), também foram observados. Nefrite intersticial linfoplasmocítica foi a alteração tubulointersticial mais frequente, visualizada em diferentes intensidades nos rins de 100% dos gatos. Os resultados do presente estudo demonstram que o tempo prolongado entre a infecção e a avaliação histopatológica pode ter sido decisivo para o surgimento das lesões renais em todos os gatos infectados pelo FIV e para o agravamento dessas lesões em alguns gatos...

The feline immunodeficiency virus (FIV) infection in domestic cats is characterized by immunological disorders that commonly manifest in a later stage of the disease. Similarly to the human immunodeficiency virus (HIV) infection in humans, FIV infection is commonly associated with opportunistic infections and progressive development of nephropathies. Therefore, the aim of the present study was to perform histological evaluation of the kidneys of 10 cats experimentally infected with FIV and euthanized at 60 months after viral inoculation. In the kidneys of 100% of the cats infected with FIV, glomerular and tubulointerstitial lesions were seen. The glomerular lesions were mainly characterized by global or segmental thickening of the glomerular basement membrane (membranous glomerulonephritis). Glomerulosclerosis, and in two cases, proliferation of intraglomerular epithelial cells (glomerular crescent) were also observed. The intersticial lymphoplasmacytic nephritis was the tubulointerstitial alteration most frequent and was observed in different intensity levels in 100% of the cats. The results of the present study demonstrate that the prolonged time between infection and histopathological evaluation may have been decisive for the arising of renal lesions in all cats infected with FIV and for the increase of these lesions in some cats...

Avaliação da albuminúria e da eletroforese de proteínas urinárias de cães com hiperadrenocorticismo e a relação com a pressão arterial sistêmica / Evaluation of albminuria and electrophoresis of urinary proteins from dogs with hyperadrenocorticism and relation with systemic arterial pressure

O hiperadrenocorticismo é uma das endocrinopatias mais comuns em cães, sendo caracterizado pela exposição excessiva de glicocorticóides secretados pelas adrenais. A hipercortisolemia crônica pode promover várias complicações, incluindo hipertensão sistêmica e glomerulonefrite. A glomerulonefrite pode desencadear variáveis graus de proteinúria e uma tendência de evolução para doença renal crônica. A perda de proteínas na urina, principalmente da albumina, é uma característica das doenças glomerulares e a determinação de variáveis laboratoriais, como a razão proteína:creatinina urinária (RPC), albuminúria (teste de ELISA) e eletroforese das proteínas urinárias, são recomendadas para a elucidação do diagnóstico. Assim, o objetivo do estudo é avaliar a relação entre proteinúria e hipertensão arterial sistêmica em cães com hiperadrenocorticismo e verificar, pela avaliação da albuminúria e do peso molecular das proteínas urinárias, o segmento do néfron que foi comprometido ou lesado. Foram avaliados 30 cães com diagnóstico de hiperadrenocorticismo, subdivididos em 13 cães com hipertensão arterial sistêmica (grupo I) e 17 cães normotensos (grupo II). Foram determinados a RPC; a albuminúria pela avaliação da albumina normalizada e razão albumina:creatinina urinária (RAC) e a eletroforese de proteínas pela técnica em gel de poliacrilamida, contendo dodecil sulfato de sódio (SDS-PAGE). Os resultados foram comparados com os dados obtidos de 30 cães clinicamente saudáveis. Foi constatado que não houve influência da hipertensão arterial sistêmica nos cães com hiperadrenocorticismo em relação à quantificação da albuminúria, determinada pelo método ELISA, e nem na qualidade e quantidade das bandas de proteínas de baixo (<60 kDa) e de alto peso molecular (>60 kDa). No entanto foi determinado que cães com hiperadrenocorticismo podem desenvolver lesões glomerulares e tubulares, caracterizadas pela presença de albuminúria e de proteínas de alto e de baixo pesos moleculares, independentemente da presença de hipertensão arterial sistêmica. Conclui-se que a avaliação quantitativa (RPC e RAC) e qualitativa (SDS-PAGE) das proteínas urinárias traz informações adicionais que indicam os possíveis segmentos comprometidos dos néfrons que causaram as perdas de proteínas na urina.

Hyperadrenocorticism is one of the commonest endocrinopathies in dogs, and it is characterized by the excessive exposure of glucocorticoids excreted by adrenals. Chronic hypercortisolemia may promote several complications, including systemic hypertension and glomerulonephritis. Glomerulonephritis may initiate several variable degrees of proteinuria and leading to the development of chronic kidney disease. The loss of proteins through urine, mainly predominant albumin, is a characteristic of glomerular diseases and the determination of laboratorial variables, such as the urinary protein-to- creatinine ratio (UPC), urinary albumin-to-creatinine ratio (UAC; ELISA test) and electrophoresis of urinary proteins are recommended to elucidate the diagnosis. Therefore, the goal of this study is to evaluate the relationship between proteinuria and systemic arterial hypertension in dogs with hyperadrenocorticism and to determine through evaluation of albuminuria and molecular weight of urinary proteins, the segment of the nephron that could be damaged. Thirty dogs with hyperadrenocorticism were evaluated and subdivided into groups; 13 dogs with systemic arterial hypertension (group I) and 17 normotensive (group II). The UPC was determined, as well as UAC and the urine protein electrophoresis by polyacrylamide gel technique, containing dodecyl sodium sulphate (SDS-PAGE). The results were compared with data obtained from 30 clinically healthy dogs. No association between systemic arterial hypertension and albuminuria was detected in dogs with hyperadrenocorticism as well as no alterations of proteins patterns or molecular weights bands of low (<60 kDa) or high molecular weight (> 60 kDa) was found. However, dogs with hyperadrenocorticism may develop glomerular and tubular injuries that were characterized by the presence of albuminuria and proteins of low and high molecular weights, independently of systemic arterial hypertension. In conclusion, the quantitative (UPC and UAC) and qualitative (SDS-PAGE) evaluation of urinary proteins could add information to indicate the possible segments of the nephrons that caused the loss of those proteins.

Renal histopathllogical findings in dogs with visceral leishmaniasis / Achados histopatológicos renais em cães com leishmaniose visceral

Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

A leishmaniose visceral acomete vários órgãos entre eles os rins; o que pode levar a insuficiência renal e a morte. Com o objetivo de verificar este acometimento renal foram avaliados materiais de 100 cães naturalmente infectados e com diagnósticos sorológicos de leishmaniose visceral canina - LVC. As alterações inflamatórias estavam presentes em 25,3% dos túbulos, em 67,0% do interstício e em 52,0% dos glomérulos. Não houve diferença significativa (p > 0,05) entre a presença de glomerulonefrite em cães sintomáticos e oligossintomáticos. As glomerulonefrites membranosa e membrano proliferativa foram as mais freqüentes, ambas com 18,0% de freqüência seguidas da glomeruloesclerose segmentar e focal com 14,0%. Foram observadas alterações como cilindrúria, hipertrofia tubular e fibrose e infiltrados inflamatórios periglomerulares e peritubulares multifocais e difusos. Os achados concordam com os de outros autores indicando que o acometimento renal é comum na LVC e que os padrões de glomerulonefrites membranoploriferativa e membranosa; assim como o acometimento tubulointersticial são freqüentes.

Light and electron microscopic analysis of consecutive renal biopsy specimens from leishmania-seropositive dogs.

Canine visceral leishmaniasis frequently causes renal damage that leads to chronic kidney disease. Fifteen dogs seropositive for Leishmania were selected and biopsied before (T0) and 60 days later after (T1) treatment with a specific anti-Leishmania pharmacological agent. Various parameters were selected for evaluating the glomerular and tubulointerstitial damage. At T0, mesangioproliferative and membranoproliferative glomerulonephritis were observed in 6 dogs, chronic glomerulosclerosis in 5, and end-stage kidney in 3; renal tissue from 1 dog was within normal histologic limits. The most frequently observed ultrastructural changes were foot-process effacement, thickening of the basement membranes, and immune deposits. One dog had mesangial immune deposits at T1 that had not been present at T0, so the diagnosis was changed to mesangioproliferative glomerulonephritis. In dogs with end-stage kidney, the number of obsolescent glomeruli and cystic atrophied glomeruli was increased at T1. However, progression of the glomerular lesions was minimal in most dogs. Worsening of tubulointerstitial scores was evident in the dogs with the most severe lesions at the first biopsy. Progression of the tubulointerstitial damage was minimal in the mildly affected dogs, and the interstitial inflammation was abated. In conclusion, renal lesions can progress over a 60-day period in canine leishmaniasis. A longer period between the renal biopsies would be necessary to demonstrate more severe changes. In addition a specific anti-Leishmania treatment could have a significant effect in the early stages of the disease.

Pathologic evaluation of canine renal biopsies: methods for identifying features that differentiate immune-mediated glomerulonephritides from other categories of glomerular diseases.

BACKGROUND: Human renal biopsies are routinely evaluated with light microscopy (LM) using a panel of histologic stains, transmission electron microscopy (TEM), and immunofluorescence (IF) microscopy to obtain a diagnosis. In contrast, the pathologic evaluation of glomerular disease in veterinary medicine has relied mostly on LM and was of limited utility. To address this problem, recently established veterinary renal diagnostic centers have adopted methods used in human nephropathology for evaluation of renal biopsies. Three broad categories of disease, which have the greatest implications for clinical management of proteinuric dogs, have been established and include amyloidosis, immune complex-mediated glomerulonephritis (ICGN), and non-ICGN. OBJECTIVE: To demonstrate histopathologic, ultrastructural, and IF findings in renal biopsy specimens that experienced veterinary nephropathologists utilize to make accurate and clinically useful diagnoses in dogs with proteinuric glomerular disease and to provide guidelines for the proper evaluation of renal biopsies. METHODS: Renal biopsy specimens were routinely examined by LM, IF, and TEM. Samples were reviewed by members of the World Small Animal Veterinary Association Renal Standardization Study Group to identify lesions that were diagnostic for, or suggestive of, the presence of immune complexes (IC) or amyloidosis in all modalities. Ten guidelines for renal biopsy evaluation were formulated. RESULTS: Each method of investigation contributed important findings that were integrated to make an accurate final morphological diagnosis. The guidelines were validated by an independent group of veterinary pathologists. CONCLUSIONS AND CLINICAL IMPORTANCE: Routine evaluation of renal biopsies with LM, TEM, and IF is feasible and necessary for making accurate, morphologic diagnoses that can be used to guide clinical management of dogs with glomerular disease.