Comparative study of chronic kidney disease in dogs and cats: Induction of myofibroblasts

We investigated the kidneys of dogs and cats to clarify whether renal myofibroblasts induction is associated with the severity of chronic kidney disease (CKD). Immunohistochemical expression of myofibroblast markers, α-smooth muscle actin (SMA) and vimentin, were evaluated quantitatively. The degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration, and interstitial fibrosis were also evaluated quantitatively. The plasma creatinine (pCre) concentrations correlated with glomerulosclerosis, cell infiltration, and fibrosis in dogs, and only with fibrosis in cats. The α-SMA expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, and with pCre and fibrosis in cats. Tubular vimentin expression correlated with fibrosis in cats, but not in dogs. Interstitial vimentin expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, but only with pCre in cats. In conclusion, it was suggested that the severity of CKD in dogs and cats was mediated by different pathways associated with myofibroblasts expression.     

Chronic renal failure in young dogs–possible renal dysplasia

The clinico-pathological findings are described in thirteen young dogs with advanced renal disease. All but three dogs were less than 2 years old. Some had signs of renal dysfunction since birth. Presenting signs were variable but anorexia, lethargy and weight loss were most frequent. All dogs had raised blood urea levels and most passed dilute urine; proteinuria and anaemia were variable findings. At necropsy all dogs had extra-renal lesions of renal failure and finely granular or lobulated, shrunken kidneys. The microscopical appearances of the kidneys were not those of amyloidosis, inflammatory or glomerular disease but were considered likely to be of developmental origin. The renal lesions were divided into three histologically distinct groups.

• 1 Predominantly cystic and connective tissue changes, characterized by striking dilatation of glomerular capsular spaces and cortical tubules.
• 2 Atypical connective tissue changes in which there were segmental bands of fibrous tissue containing primitive glomerular and tubular structures.
• 3 Predominantly glomerular and connective tissue changes, characterized by varying degrees of glomerulosclerosis and widespread calcification of glomeruli, tubules and blood vessels.

All groups had cortical and medullary interstitial fibrosis but minimal inflammatory cell infiltrates.     

Progressive renal disease in Soft-coated Wheaten Terriers: possible familial nephropathy

Clinical and pathological features are described in seven young Soft-coated Wheaten Terriers with chronic renal disease. The oldest dog was 21/2 years; in the other six, ages at death ranged from one to 15 months. Two of the puppies were littermates: one died at 4 weeks, the other at 12 months. Two of the dogs were examined at intervals up to 14 months, during which time there was progressive deterioration in renal function. All seven dogs had abnormal kidneys with cortical narrowing. The histological features were not consistent and included: tubular dilatation and basement membrane thickening; an unusually large proportion of immature glomeruli; persistence of interstitial connective tissue resembling foetal mesenchyme. Inflammatory change was minimal except in two dogs with super-imposed pyelonephritis. The clinical and laboratory data suggest that these dogs had dysplasia of the kidneys that progressed to chronic renal disease during early life. In three dogs there was a familial relationship.     

Correlation of electrophoretic urine protein banding patterns with severity of renal damage in dogs with proteinuric chronic kidney disease

Background

Urine protein loss is common in dogs with chronic kidney disease (CKD). Currently available noninvasive means of evaluating CKD in dogs cannot accurately predict the severity of glomerular and tubulointerstitial damage. Electrophoretic analysis of urine proteins can indicate the compromised renal compartment (glomerular vs tubular), but extensive evaluation of protein banding pattern associations with histologic damage severity has not been performed in dogs.

Objectives

We aimed to evaluate electrophoretic banding patterns as indicators of the presence and severity of glomerular and tubulointerstitial damage in dogs with naturally occurring, predominantly proteinuric CKD.

Methods

We performed a retrospective study using urine and renal tissue from 207 dogs with CKD. Urine protein banding patterns were correlated with histologic severity of renal damage. Sensitivity and specificity of banding patterns for the detection of glomerular and tubulointerstitial damage were determined.

Results

Banding patterns were 97% sensitive and 100% specific for the detection of glomerular damage and 90% sensitive and 100% specific for the detection of tubulointerstitial damage. Correlations between composite banding patterns and the severity of renal damage were strong, while glomerular banding patterns correlated moderately with glomerular damage severity, and tubular gel scores correlated weakly to moderately with the severity of tubulointerstitial damage.

Conclusions and clinical importance

Urine protein banding patterns are useful for the detection of glomerular and tubulointerstitial damage in dogs with proteinuric CKD.     

Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers

Background: Proteinuria is a feature of pyometra‐associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. Objectives: To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers. Animals: Forty‐seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. Methods: Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C‐reactive protein, urinary thromboxane B₂) and tubular function (urinary retinol‐binding protein, urinary N‐acetyl‐β‐d ‐glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 2+ or 3+ were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs. Results: UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05–8.69) compared with healthy bitches (0.08, 0.02–0.16) (P < .01). Twenty‐two of 47 dogs with pyometra had UPC>0.5, 12 had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile. Conclusion: Dogs with pyometra and UPC>1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra‐associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis in dogs.     

Juvenile nephropathy in a Boxer dog resembling the human nephronophthisis-medullary cystic kidney disease complex

A juvenile nephropathy in a 4-year-old male Boxer dog, closely resembling the Nephronophthisis (NPHP)-Medullary Cystic Kidney Disease Complex (MCKD) in humans is described. Gross examination of the kidneys revealed several multiple cysts at the corticomedullary junction and in the medulla. Histological examination was characterized by a widespread tubular atrophy and dilatation, with a marked thickening of the tubular basement membrane, interstitial lymphocytic infiltration and fibrosis. Ultrastructural studies revealed dilated tubules with irregular basement membrane thickening and splitting. Lectin histochemistry investigation revealed that the cysts originated in the distal convoluted tubule and collecting duct. Having excluded all other known cystic diseases of the kidney, and based on the lectin histochemistry results, the macroscopic and histological findings of our case are highly compatible with a diagnosis of the NPHP-MCKD complex. To our knowledge, this is the first report describing this particular lesion.     

Microscopic features of canine renal dysplasia

Forty-five cases of renal dysplasia in dogs are examined. Microscopic lesions of dysplasia include asynchronous differentiation of nephrons, persistent mesenchyme, persistent metanephric ducts, atypical tubular epithelium, and dysontogenic metaplasia. These may be distinguished from secondary lesions including compensatory hypertrophy and hyperplasia of the nephron and a variety of degenerative and inflammatory lesions. Although morphological features of renal dysplasia in dogs differ somewhat from those in man, microscopic criteria used in the diagnosis of human dysplasia may be useful when applied to the dog.     

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.     

A comparative study of chronic kidney disease in dogs and cats: induction of cyclooxygenases

The present study investigated whether renal cyclooxygenase (COX) induction is associated with the severity of chronic kidney disease (CKD) in dogs and cats. The collected kidneys were examined histopathologically and immunohistochemically. The immunoreactivities of COX-1 and COX-2 were evaluated quantitatively, and the correlations to the plasma creatinine concentrations, glomerular size, glomerulosclerosis, interstitial fibrosis, and interstitial cell infiltration were evaluated statistically. Immunoreactivities for COX-1 were heterogeneously observed in the medullary distal tubules and collecting ducts; no correlations with the severity of renal damage were detected. Immunoreactivities for COX-2 were heterogeneously observed in the macula densa (MD) regions. In dogs, the percentage of COX-2-positive MD was significantly correlated with the glomerular size. In cats, glomeruli with COX-2-positive MD had significantly higher sclerosis scores than those with COX-2-negative MD. In conclusion, renal COX-2 is induced in canine and feline CKD, especially in relation to the glomerular changes.     

Bilateral fusion of a supernumerary kidney in a cat

A rare case of bilateral fusion of a supernumerary kidney was found during the necropsy of a female, 8-year-old, mixed breed cat that died as a result of azotemia and chronic enteritis. Apart from enteritis, necropsy revealed four kidneys, two in the sublumbar left region and two in the sublumbar right region, with cortical and medullary regions well individualized and independent; however, the pelvis was partially fused, giving rise to a single ureter. The kidneys were small, whitish and firm, with irregular surfaces. Microscopically, all kidneys displayed normal renal glomeruli and tubules among the immature renal glomeruli and tubules with characteristics of hypoplasia. Foci of glomerulosclerosis, nephrocalcinosis and interstitial fibrosis were also observed.     

Positive correlation between renal tubular flattening and renal tubular injury/interstitial fibrosis in murine kidney disease models

The number of patients with chronic kidney disease (CKD) is growing continuously globally. In order to study pathogenesis and mechanisms, many animal models have been developed, including spontaneous, genetic, and induced models. Although each type of CKD shows disease-specific tissue changes in the early stages, tubular disorder and interstitial fibrosis histologically occur in the course of progression to end-stage renal failure. Therefore, the quantification of tubular disorder and interstitial fibrosis in CKD research using animal models is essential for measuring the degree of CKD severity and, thus, efficacy of therapeutic agents. Several strategies have been used to quantify interstitial fibrosis. Among scoring factors, renal tubular flattening can be quantitatively evaluated easily and inexpensively. However, the diagnostic value of renal tubular flattening evaluation has not been investigated previously. Therefore, in this study, we investigated the correlation between renal tubular flattening and interstitial fibrosis or renal tubular injury markers. We observed a strong correlation between the degree of tubular injury/interstitial fibrosis and renal tubular flattening in three types of mouse renal disease model. This is advantageous because rapidly advancing technologies such as artificial intelligence and image processing can be easily applied; hence, a more precise, objective, and quantitative diagnosis should be possible in the future.     

B-mode and Doppler ultrasound of chronic kidney disease in dogs and cats

Ultrasound is the imaging test of choice for renal evaluation, because it provides information about the position, size, shape, internal architecture and hemodynamics of the kidneys without harming the patient. In chronic kidney disease, the main findings observed in B-mode ultrasound images are increased cortical echogenicity, loss of corticomedullary differentiation, reduced renal volume and irregular renal contour, and when these changes are associated, they are indicative of end-stage renal disease. However, the cause of kidney disease cannot be determined by ultrasonography, but must be confirmed by means of biopsy, although the presence of ultrasonographic changes indicative of the end-stage of the disease may contraindicate this procedure. The Doppler ultrasound test complements the ultrasonic B-mode examination and enables the assessment of renal perfusion based on a calculation of the hemodynamic indices, which are increased in cases of chronic kidney lesions, with higher values ??in the most severe cases. Thus, ultrasound examinations are not only useful in diagnostics but also play an important role in defining the prognosis of patients with chronic kidney disease.     

Glomerular deposition of immune complexes in dogs following natural infection with canine adenovirus.

The renal lesions were studied in eight dogs which had either died as a result of acute canine adenovirus infection (Rubarth's disease) or were in various stages of recovery from the clinical disease. Using immunofluorescence techniques granular deposits of IgG were detected in the glomeruli of six dogs; four of these animals had similar glomerular deposits of canine adenovirus antigen. Eluates obtained from kidney tissue of four dogs were found to contain antiviral antibody. Histologically those animals in which glomerular deposits of IgG and viral antigen were detected showed segmental glomerular hypercellularity. These findings were attributed to the deposition of circulating virus antigen-antibody complexes in the glomeruli.     

Juvenile nephropathy in 37 boxer dogs

OBJECTIVES: The purpose of this study was to review and characterise the clinical presentation of young boxer dogs with chronic kidney disease referred to the authors' institutions. METHODS: Records were collected retrospectively from 37 boxer dogs, less than five years of age, which had presented with azotaemia, inappropriately low urine concentrating ability, and ultrasound or radiographic evidence of abnormal kidneys. RESULTS: Clinicopathological findings included azotaemia, hyperphosphataemia, anaemia, isosthenuria and proteinuria. Ultrasonographic findings included hyperechoic renal cortices, loss of corticomedullary junction definition, dilated pelves and irregularly shaped small kidneys. Renal histopathological findings included pericapsular and interstitial fibrosis, inflammatory cell infiltration, dilated tubules, sclerotic glomeruli and dystrophic calcification. Survival time of the dogs varied from zero to over five years after diagnosis. CLINICAL SIGNIFICANCE: This paper documents features of the presentation and progression of juvenile nephropathy in boxer dogs. While juvenile nephropathy has been reported in individual cases of boxer dogs previously, this is the first reported case series.     

Effects of T lymphocytes, interleukin-1, and interleukin-6 on renal fibrosis in canine end-stage renal disease

Canine end-stage renal disease (ESRD) is defined as the almost complete failure of renal function or irreversible destruction and is characterized by extensive glomerular sclerosis, tubular atrophy, interstitial inflammation, and fibrosis. Renal fibrosis is a common pathway leading to kidney failure. Infiltrating immunocytes in the end-stage kidney and several related factors are involved in renal fibrogenesis. A total of 18 renal tissue samples were obtained from canine patients with ESRD using biopsy and necropsy procedures. The extent of renal fibrosis was histopathologically examined by Masson trichrome staining. T-cell and B-cell localization and macrophage lineages were determined by immunohistochemical staining. Additionally, interleukin-1 (IL-1), IL-2, and IL-6 levels in the canine ESRD kidney were immunohistochemically evaluated and compared with expression patterns in the normal kidney. Significant fibrosis and infiltrating immunocytes consistent with lymphocytes were observed. Although the B-cell count was increased in the end-stage kidney, immunostaining patterns disclosed a marked increase in the number of CD3(+) cells. Furthermore, the remarkable increase in IL-1 and IL-6 levels suggests that T cells in the kidneys of dogs with ESRD spontaneously express these cytokines. In this study, the correlation between the degree of renal fibrosis and cytokines in canine ESRD was examined. The present study shows that T lymphocytes and IL-6 play important roles in renal fibrosis.     

Pyelonephritis in slaughter pigs and sows: Morphological characterization and aspects of pathogenesis and aetiology

Background

Pyelonephritis is a serious disease in pig production that needs to be further studied. The purpose of this study was to describe the morphology, investigate the pathogenesis, and evaluate the aetiological role of Escherichia coli in pyelonephritis in slaughtered pigs by concurrent bacteriological, gross and histopathological examinations.

Methods

From Danish abattoirs, kidneys and corresponding lymph nodes from 22 slaughtered finishing pigs and 26 slaughtered sows with pyelonephritis were collected and evaluated by bacteriology and pathology. Based on gross lesions, each kidney (lesion) was grouped as acute, chronic, chronic active, or normal and their histological inflammatory stage was determined as normal (0), acute (1), sub-acute (2), chronic active (3), or chronic (4). Immunohistochemical identification of neutrophils, macrophages, T-lymphocytes, B-lymphocytes, plasma cells, E. coli and Tamm-Horsfall protein (THP) in renal sections was performed. The number of E. coli and the proportion of immunohistochemically visualized leukocytes out of the total number of infiltrating leukocytes were scored semi-quantitatively.

Results

Lesions in finishing pigs and sows were similar. Macroscopically, multiple unevenly distributed foci of inflammation mostly affecting the renal poles were observed. Histologically, tubulointerstitial infiltration with neutrophils and mononuclear cells and tubular destruction was the main findings. The significant highest scores of L1 antigen⁺ neutrophils were in inflammatory stage 1 while the significant highest scores of CD79αcy⁺ B-lymphocytes, IgG⁺ and IgA⁺ plasma cells were in stage 3 or 4. Neutrophils were the dominant leukocytes in stage 1 while CD3ε⁺ T-lymphocytes dominated in stage 2, 3 and 4. Interstitially THP was seen in 82% and 98% of kidneys with pyelonephritis from finishing pigs and sows, respectively. E. coli was demonstrated in monoculture and/or identified by immunohistochemistry in relation to inflammation in four kidneys from finishing pigs and in 34 kidneys from sows.

Conclusions

E. coli played a significant role in the aetiology of pyelonephritis. Neutrophils were involved in the first line of defence. CD3ε⁺ T-lymphocytes were involved in both the acute and chronic inflammatory response while a humoral immune response was most pronounced in later inflammatory stages. The observed renal lesions correspond with an ascending bacterial infection with presence of intra-renal reflux.     

Renal medullary amyloidosis in Dorcas gazelles

Between January 1976 and September 1987 renal medullary amyloidosis (RMA) was diagnosed in 17 Dorcas gazelles; the necropsy prevalence rate was 17/32 (53%). The most severe amyloid deposits were in the renal medulla; glomeruli were spared. Renal cortical lesions of interstitial fibrosis and tubular atrophy and dilatation significantly correlated with RMA (P less than 0.01) and were considered to be secondary changes. There were varying degrees of lymphoplasmacytic inflammation and tubular cast formation which did not significantly correlate with RMA. Amyloid was confirmed histochemically and by electron microscopy and was identified as AA type by the permanganate method. Progressive renal failure was the cause of death or necessitated euthanasia in 7/17 (41%) gazelles. RMA in Dorcas gazelles does not appear to be familial. A high prevalence of chronic or recurring Actinomyces (Corynebacterium) pyogenes infections may be an important factor.     

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.     

In vivo cell tracking of canine allogenic mesenchymal stem cells administration via renal arterial catheterization and physiopathological effects on the kidney in two healthy dogs

Stem cell therapy is being special premise for various renal diseases. However, there is limited literature on localization and pathologic and functional effects of allogenic mesenchymal stem cells (MSCs) in healthy dogs. Two healthy dogs were included in this study. Canine MSCs (cMSCs) were cultured from canine bone marrow and incubated with superparamagnetic iron oxide (SPIO) for in vivo cell tracking via MR imaging. The dogs were given the MSC (3 × 10(6) cells) into a renal artery via femoral artery catheterization. Follow-up serial renal assessments included ultrasonography and MRI, serum chemistry, urine analysis, and renal clearance tests. The dogs were euthanized at days 8 and 35 respectively for histopathologic evaluation of kidney. Strong hypointensity in MRI was detected in the treated renal cortex the day after cMSCs infusion. However they disappeared from MR image by the 8th day. Of the serum chemistry tests, serum hepatic enzymes (ALT, AST) were significantly elevated for one week after cMSCs treatment. Histopathological findings also revealed infiltration of SPIO-containing cells into the parenchyma of kidney. On 35th day, histopathology, glomerular atrophy, tubular necrosis, and mineralization were found in the subcapsular cortex, with fibrosis of the interstitial tissues. In vivo MRI studies of stem cells were useful in determining the sequential location of stem cells in the renal parenchyma of healthy dogs. Allogenic stem cells administered via renal artery caused inflammation, tubular necrosis, mineralization, and fibrosis without functional complications.     

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

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