Acellular fish skin may be used to facilitate wound healing following wide surgical tumor excision in dogs: a prospective case series.

OBJECTIVE: To prospectively evaluate clinical outcomes using acellular fish skin grafts (FSGs) for the management of complete wound healing by secondary intention after wide surgical excision of skin tumors in dogs. ANIMALS: 5 dogs undergoing wide surgical excision of skin tumors on the distal extremity. CLINICAL PRESENTATION AND PROCEDURES: FSGs were applied to surgical wound beds following wide excision of the tumor. Bandages were changed weekly and additional grafts placed when integration of the previous graft was complete. The wounds were assessed for the following: dimensions, tissue health (color), time to complete epithelialization, complications, and tumor recurrence. RESULTS: All masses were excised with 2-cm lateral margins and 1 fascial plane deep to the tumor. Tumor diagnoses included 3 mast cell tumors and 2 soft tissue sarcomas. Surgical wounds had a median area of 27.6 cm2 (range, 17.6 to 58.7 cm2). The median number of FSG applications was 5 (range, 4 to 9 applications). Complete epithelialization occurred within 7 to 9 weeks for uncomplicated wounds (3 of 5) and 12 to 15 weeks for complicated wounds (2 of 5) that sustained self-trauma. There were no adverse events related to the use of FSGs. Local recurrence was not seen over a follow-up period ranging from 239 to 856 days. CLINICAL RELEVANCE: Wide surgical excision of distal extremity skin tumors, followed by repeated application of acellular FSGs, resulted in complete healing of all wounds with no adverse events. This treatment method does not require advanced reconstructive surgical skills and may be useful for the management of skin tumors on the distal extremities.

Clinicopathologic characteristics, pathology, and prognosis of 77 dogs with focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of nonimmune complex glomerulopathy and the prognosis and clinicopathologic findings associated with this condition have not been described in dogs. OBJECTIVE: To characterize the presentation and identify clinical factors associated with the survival of dogs with FSGS. ANIMALS: Seventy-seven dogs diagnosed with FSGS based on evaluation of renal biopsy samples submitted to the International Veterinary Renal Pathology Service. METHODS: Retrospective review of medical records of dogs biopsied for evaluation of proteinuria between January 2015 and May 2017. RESULTS: The incidence of FSGS among all dogs biopsied for proteinuria was 26%. Significantly more females (48; 62.3%) than males (29; 37.7%) were affected (P = .04). At the time of biopsy, median serum creatinine concentration (SCr) was 1.2 mg/dL (range, 0.3-8.7), median serum albumin concentration (Alb) was 2.8 g/dL (range, 1.1-4.6), median systolic blood pressure was 153.5 mm Hg (range, 95-260), and median urine protein : creatinine ratio was 5.9 (range, 1.4-22). Median survival time after biopsy was 258 days (range, 26-1003) for dogs that died from all causes (n = 32). Factors that were associated with a shorter survival time included SCr ≥ 2.1 mg/dL (P < .01) and Alb < 2 g/dL (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Most dogs with FSGS were female, and although commonly hypertensive, azotemia, severe hypoalbuminemia and ascites or edema were observed infrequently. Variables significantly associated with survival time were SCr and Alb.

Chronic Renal Changes After a Single Ischemic Event in an Experimental Model of Feline Chronic Kidney Disease.

Previous work demonstrated renal fibrosis 70 days after a single unilateral in vivo renal ischemic event, but changes associated with a single episode of renal ischemia past this time are unknown. In this study, we evaluated renal function and structural changes 6 months after a 90-minute in vivo unilateral renal ischemic event. Six adult female cats underwent unilateral renal ischemia and renal function was followed for 6 months, at which time the kidneys were evaluated by histology and histomorphometry. Over time, there was a significant reduction in the glomerular filtration rate and an elevation of serum creatinine of 31% and 42%, respectively. All cats had tubulointerstitial lesions characterized by segmental interstitial inflammation, tubular atrophy, and interstitial fibrosis. Unlike short-term studies, ischemic kidneys had variable numbers of obsolescent glomeruli, consistent with the development of atubular glomeruli and subsequent ischemic glomerulosclerosis. Chronic changes associated with acute renal ischemia may include loss of function and glomerulosclerosis.

Glomerulosclerosis in transgenic rabbits with ubiquitous Venus protein expression.

Focal segmental glomerulosclerosis (FSGS) is a potential cause of nephrotic syndrome both in humans and pet mammals. Glomerulopathy was reported earlier in green fluorescent protein (GFP) transgenic (TG) mice, but glomerulosclerosis has not been examined in GFP TG rabbits so far. In the present study, the potential manifestation of FSGS was investigated in both Venus TG rabbits generated by Sleeping Beauty (SB) transposition and age-matched control New Zealand White (NZW) rabbits. Venus protein fluorescence was detected by confocal microscopy and quantified by microplate reader. Urinalysis, haematology, serum biochemistry and renal histology were performed to assess the signs of FSGS. Higher levels of Venus fluorescence were determined in renal cortex samples than in the myocardium by both methods. Urinalysis revealed proteinuria in Venus heterozygote TG bucks, while Venus homozygote TG bucks developed microscopic haematuria. Supporting the urinalysis data, the histological findings of FSGS (glomerulomegaly and sclerotic glomeruli) were observed in renal cortex sections of Venus TG rabbits. Taken together, Venus TG bucks were diagnosed with FSGS; thus, this type of glomerulopathy could be a common disease in TG animals overexpressing GFP.

Focal Segmental Glomerulosclerosis in Related Miniature Schnauzer Dogs.

Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs in particular. This study describes the morphologic features present in the kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS, characterized by solidification of portions of the capillary tuft, affected 32% to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in older dogs. Seven of 8 dogs had arteriolar hyalinosis. Ultrastructurally, all dogs had evidence of a podocytopathy in the absence of electron-dense deposits, glomerular basement membrane splitting, or fibrils. All dogs had multifocal to extensive podocyte foot process effacement. Other podocyte changes included microvillous transformation, the presence of vacuoles or protein resorption droplets, cytoplasmic electron-dense aggregates, and occasional binucleation. Variable amounts of intraglomerular lipid were present in all dogs. All dogs were proteinuric, with measured values for the urine protein-to-creatinine ratio ranging from 1.2 to 6.5. Azotemia was mild to absent and dogs were euthanatized at 5.1 to 14 years of age, in all cases due to nonrenal diseases. The underlying cause of FSGS in these Miniature Schnauzer dogs has yet to be determined, but contributors likely include genetic podocytopathy, lipid abnormalities, and glomerular hypertension.

Fatal proteinuric kidney disease in a 30-month-old German Fleckvieh heifer caused by unilateral focal segmental glomerulosclerosis subsequent to a non-functional counterpart kidney.

INTRODUCTION: A case of secondary focal segmental glomerulosclerosis (FSGS) in a heifer is presented. A 30-month-old female German Fleckvieh heifer showed deterioration of the general condition, a poor nutritional status, proteinuria, hypoalbuminemia, and renal azotemia. Pathologically, it was diagnosed with unilateral hydronephrosis, and contralateral renal fibrosis with numerous cysts. Histologically, the fibrotic kidney showed FSGS, hyaline reabsorption droplets in proximal tubular epithelial cells, interstitial fibrosis, and tubulointerstitial inflammation. Apart from that, thrombotic microangiopathy (TMA) was seen in few renal arteries and meningeal arterioles. Pathogenesis of FSGS secondary to unilateral renal parenchymal loss (hydronephrosis) and TMA is discussed.

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.

Characterization of Proteinuria in Dogue de Bordeaux Dogs, a Breed Predisposed to a Familial Glomerulonephropathy: A Retrospective Study.

Dogue de Bordeaux dog has been reported to be predisposed to a familial glomerulonephropathy that displays some morphological modifications reported in focal and segmental glomerulosclerosis. Prevalence of quantitatively abnormal renal proteinuria was recently reported to be 33% in this breed. The nature of the proteinuria was assessed by sodium dodecyl sulfate-agarose gel electrophoresis and determinations of urinary markers (urinary retinol-binding protein, urinary N-acetyl-ß-glucosaminidase, urinary albumin and urinary immunoglobulin G) on stored specimens. Diagnostic performances of sodium dodecyl sulfate-agarose gel electrophoresis to identify dogs with elevated urinary biomarkers were assessed. Samples from 102 adult Dogue de Bordeaux dogs (47 non-proteinuric [urine protein-to-creatinine ratio ≤ 0.2], 20 borderline-proteinuric [0.2< urine protein-to-creatinine ratio ≤ 0.5] and 35 proteinuric dogs [urine protein-to-creatinine ratio >0.5]) were used, of which 2 were suffering from familial glomerulonephropathy. The electrophoretic protein patterns, for all but one proteinuric dog, were indicative of a glomerular origin and, in all dogs, the urinary albumin concentration related to creatinine concentration and the urinary immunoglobulin G concentration related to creatinine concentration were above the upper limit of the reference interval established for the breed. Sensitivity and specificity of sodium dodecyl sulfate-agarose gel electrophoresis identifying dogs with elevated urinary albumin concentration were 94% and 92%, respectively, while diagnostic performance of sodium dodecyl sulfate-agarose gel electrophoresis in detecting dogs with elevated urinary immunoglobulin G concentration yielded sensitivity and specificity of 90% and 74%, respectively. These results suggest that all proteinuric and some borderline-proteinuric Dogue de Bordeaux dogs likely have underlying glomerular lesions and that sodium dodecyl sulfate-agarose gel electrophoresis and urinary markers might be useful to screen dogs with borderline-proteinuria. Additional investigations are warranted to assess if these findings are related to the familial glomerulonephropathy.

Severe renal failure in a dog resembling human focal segmental glomerulosclerosis.

A case of renal disease in a dog resembling human focal segmental glomerulosclerosis is presented. A kidney biopsy from this animal showed focal glomerular sclerosis, with variable distribution, affecting the perihilar and peripheral segments of the glomerular tuft. Non-sclerotic glomeruli were markedly enlarged. Interstitial fibrosis in association with tubular atrophy affected approximately 20% of the area of the biopsy. Immunofluorescence labelling showed immunoglobulin M deposits entrapped in segmental sclerotic areas and ultrastructural examination revealed segmental sclerosis and obliteration of capillaries, vacuolation of podocytes and diffuse effacement of foot processes. The dog was humanely destroyed 1 month later. At necropsy examination there was severe end-stage kidney disease with interstitial fibrosis involving more than 60% of the renal tissue. The clinical course and the microscopical, immunofluorescence and ultrastructural findings in this case have similarity to focal segmental glomerulosclerosis in man.

Familial glomerulonephropathy in the Bullmastiff.

Glomerular disease was diagnosed by histopathologic examination in 11 related Bullmastiff dogs, and clinical and laboratory data were collected retrospectively. Four female and seven male dogs between the ages of 2.5 and 11 years were affected. Clinical signs, including lethargy and anorexia, were nonspecific and occurred shortly before death or euthanasia. In five affected dogs serial blood samples were obtained, and dramatically elevated blood urea nitrogen and creatinine levels were demonstrated up to 2.75 years before death. Protein-creatinine ratios were elevated in six of six dogs and were above normal 3.5 years before death in one dog. The kidneys appeared grossly normal to slightly smaller than normal at necropsy. Histologic abnormalities of the kidneys were consistent with chronic glomerulonephropathy with sclerosis. Examination of the pedigrees of related affected dogs yielded evidence supporting an autosomal recessive mode of inheritance.

Changes in quantitative profile of extracellular matrix components in the kidneys of rats with adriamycin-induced nephropathy.

Extracellular matrix components (ECMs) in histological sections of the kidney cortex from the rats with adriamycin (ADR)-induced nephropathy (5 mg/kg, i.v.) were quantified by an immunohistochemical micromethod. Changes in kidney histopathology and urine and blood biochemistry were investigated. Enlarged kidneys were granular on the surface and pale in color in ADR-treated rats, and these rats had kidneys with glomeruli with expanded mesangial area and with capillary aneurysm. Severe albuminuria, hypoalbuminemia, hypercholesterolemia and disorders in other nephrotic parameters were observed in ADR-treated rats. Type I and IV collagens, fibronectin and laminin contents in the renal cortex of ADR-treated rats at 10 weeks were 329, 317, 263 and 295%, respectively, higher than in each vehicle control, and those at 28 weeks were 1,211, 930, 1,057 and 1,012%, respectively. The glomerular sclerotic abnormalities progressed in a time-dependent manner. Moreover, there was a strong correlation between the ECM levels and serum creatinine and blood urea nitrogen levels. In conclusion, microquantification provided useful information for accurate diagnosis and prognosis of nephrotic lesions and is a good tool to assess the advancement of renal disorders in patients with nephropathy.

Diseases of captive cheetahs (Acinonyx jubatus jubatus) in South Africa: a 20-year retrospective survey.

As part of an ongoing study to determine the basis for high prevalences of veno-occlusive disease, glomerulosclerosis, and chronic lymphoplasmacytic gastritis in cheetahs, a retrospective pathology survey of captive cheetahs in the Republic of South Africa (RSA) was conducted. The RSA population was selected because its genetic composition and captive management were similar to those of the cheetah population in U.S. zoos, in which these diseases are common. For this study, archived pathology materials at the University of Pretoria Faculty of Veterinary Sciences in Onderstepoort and the Faculty of Veterinary Science, MEDUNSA, from 69 cheetahs that died between 1975 and 1995 were reviewed, and prevalences of common lesions were compared with those in the U.S. population. Gastritis associated with Helicobacter-like organisms was the most prevalent disease, accounting for close to 40% of the mortalities, including several cheetahs < 3 yr old. Glomerulosclerosis and veno-occlusive disease also were major causes of mortality in RSA cheetahs. RSA cheetahs also had adrenal cortical hyperplasia, cardiac fibrosis, lymphocytic depletion of the spleen, systemic amyloidosis, and splenic myelolipomas. The presence in the captive RSA cheetah population of the same unusual diseases that are common in U.S. cheetahs suggests a species predilection to develop these diseases in captivity.

Rhesus macaques infected with macrophage-tropic simian immunodeficiency virus (SIVmacR71/17E) exhibit extensive focal segmental and global glomerulosclerosis.

We previously showed that inoculation of rhesus macaques with molecularly cloned lymphocytetropic simian immunodeficiency virus (SIVmac239) results in SIV-associated nephropathy (SIVAN) and that the glomerulosclerotic lesions were associated with the selection of macrophagetropic (M-tropic) variants (V. H. Gattone et al., AIDS Res. Hum. Retroviruses 14:1163-1180, 1998). In the present study, seven rhesus macaques were inoculated with M-tropic SIVmacR71/17E, and the renal pathology was examined at necropsy. All SIVmacR71/17E-infected macaques developed AIDS, and most developed other systemic complications, including SIV-induced encephalitis and lentivirus interstitial pneumonia. There was no correlation between the length of infection (42 to 97 days), circulating CD4(+) T-cell counts, and renal disease. Of the seven macaques inoculated with SIVmacR71/17E, five developed significant mesangial hyperplasia and expansion of matrix and four were clearly azotemic (serum urea nitrogen concentration of 40 to 112 mg/dl). These same five macaques developed focal segmental to global glomerulosclerotic lesions. Increased numbers of glomerular CD68(+) cells (monocytes/macrophages) were found in glomeruli but not the tubulointerstitium of the macaques inoculated with SIVmacR71/17E. All macaques had glomerular deposits of immunoglobulin G (IgG), IgM, and tubuloreticular inclusions, and six of seven had IgA deposition. However, there was no correlation between the presence of circulating anti-SIVmac antibodies, immunoglobulin deposition, and glomerular disease. Tubulointerstitial infiltrates were mild, with little or no correlation to azotemia, while microcystic tubules were evident in those with glomerulosclerosis or azotemia. The four most severely affected macaques were positive for diffuse glomerular immunostaining for viral core p27 antigen, and there was intense staining in the glomeruli of the two macaques with the most severe glomerulosclerosis. Viral sequences were isolated from glomerular and tubulointerstitial fractions from macaques with severe glomerulosclerosis but only from the tubulointerstitial compartment of those that did not develop glomerulosclerosis. Interviral recombinant viruses generated with env sequences isolated from glomeruli confirmed the M-tropic nature of the virus found in the glomeruli. The correlation between the increased number of CD68(+) cells (monocytes/macrophages) in the glomeruli, the localization of p27 antigen in the glomeruli, and the glomerular pathology confirms and extends our previous observations of an association between glomerular infection and infiltration by M-tropic virus and SIVAN.

Focal mesangial-sclerosing glomerulonephritis and acute-spontaneous infectious canine hepatitis: structural, immunohistochemical and subcellular studies.

The glomerular alterations observed in a dog with acute spontaneous infectious canine hepatitis (ICH) are described. Histologic changes of the glomeruli were enlargement of the mesangium with presence of intranuclear inclusion bodies and without proliferation of mesangial cells. Electron microscopy revealed adenovirus replication sites in glomerular mesangial cells and in endothelial cells of glomerular capillaries, as well as a focal mesangial-sclerosing glomerulonephritis associated with electron dense deposits which were closely related with extracellular ICH viral particles and immunohistochemically reactive for immunoglobulin (Ig) G, IgA, IgM and C3c complement components.

Proteinuria associated with glomerulosclerosis and glomerular collagen formation in three Newfoundland dog littermates.

Three dogs out of a litter of eight Newfoundland dogs developed a progressive fatal glomerulopathy. The affected dogs were a 2-month-old male, a 2.5-month-old female, and a 1-year-old male. The disease in all three animals was characterized by growth retardation, anorexia, proteinuria (14-16 g/liter), hypoalbuminemia (15-21 g/liter, elevated plasma urea (13-28 mmol/liter), and creatinine (83-296 mumol/liter) concentrations. Because of a bad prognosis the dogs were euthanatized. On postmortem examination, the animals had enlarged, slightly pale kidneys, which revealed glomerulosclerosis and glomerulofibrosis on histologic and electron microscopic examination. The lesions consisted of subendothelial and mesangial collagen fibrils and an increase of mesangial matrix. The fibrosis may result from endothelial or mesangial collagen formation as the manifestation of a metabolic disease.

[Age-related non-tumorous lesions in SPF C57BL/6 mice with special reference to amyloidosis].

Non-tumorous pathological changes in C57BL/6 CrSlc mice, which were reared under a barrier system and died spontaneously, were examined. At 3 months intervals 125 to 209 mice were purchased at 4 weeks of age and raised for the supply of aged animals. A large portion of the mice were used for various experiments between 3 and 30 months of age, while not a small number died spontaneously and were autopsied. The major non-neoplastic lesion was amyloidosis, with incidence of 55.5% and 74.4% for the autopsied female and male, respectively. The organs involved were the liver, kidneys, spleen, adrenal glands, ileum, heart and lungs. Skin ulceration and its scar, cerebral vascular calcification, glomerulosclerosis and sepsis in both sexes, distension of the seminal vesicles in males, fibroblast growth of the adrenal glands in females were commonly found. Incidence of spontaneous neoplastic lesions was 69.7% and 55.1% for the female and male, respectively.

Analysis of renal immune-deposits in canine leishmaniasis. Preliminary results.

Previous studies carried out on 34 dogs spontaneously infected by Leishmania infantum showed the presence of kidney lesions characterized by immunologically mediated glomerular and tubular damage. Glomerular immune-deposits were studied in 13 of these dogs. Immunoglobulins were isolated from kidney tissues by acid elution; IgG fractions from eluates, obtained by ammonium sulfate precipitation, were subjected to clonotypic analysis by autoradiography after isoelectrofocusing (IEF) using 125I radiolabelled goat IgG fraction-anti Fab2 of dog IgG. Idiotypic characterization of IgG eluted from kidney tissues was performed by IEF and autoradiography using both 125I radiolabelled membrane antigens of L. infantum extracted by Triton x 100 and 125I radiolabelled dog IgG for rheumatoid or anti-idiotypic activity. The IgG deposited in the kidney tissues of examined dogs were polyclonal and a specific activity against Leishmania membrane antigens was revealed. Meanwhile an anti-IgG activity of deposited immunoglobulins was not observed.

Spontaneous renal disease in dogs.

Renal disease is common in dogs. The incidence of significant renal disease increases with age. Many disease processes are subtle and subacute, and so many are not detected until they result in chronic renal failure. The causes of many renal diseases are not known but one must suspect immune-mediated damage in some.