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In collaboration with the American College of Veterinary Pathologists

In collaboration with the American College of Veterinary Pathologists

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

A 4-year-old male neutered domestic shorthair cat was presented to The Ohio State University College of Veterinary Medicine for a 2-month history of severe weight loss, lethargy, anemia, and bilaterally hyperechoic kidneys with loss of corticomedullary distinction as reported by the referring veterinarian. Relevant initial laboratory results included severe non-regenerative normocytic hypochromic anemia, increased blood urea nitrogen, minimally concentrated urine, proteinuria, and an increased urine protein:creatinine ratio. Cytologic evaluation of a bone marrow aspirate revealed a markedly hypocellular marrow with abundant mucinous material. Gelatinous marrow transformation (GMT) was confirmed histologically by the presence of mucinous material in the bone marrow that stained positive for Alcian blue but negative for periodic acid-Schiff. The cat died despite repeated blood transfusions and supportive care. Gelatinous marrow transformation, immune complex-mediated membranoproliferative glomerulonephritis, and gastrointestinal hemorrhage were observed on autopsy and histology. It is likely that the development of GMT was secondary to chronic kidney disease (CKD) and that CKD, GMT, and gastrointestinal hemorrhage contributed to the cat's non-regenerative anemia.

Refractometry is utilized routinely to evaluate canine urine specific gravity (USG) in veterinary clinical settings. We aimed to determine if the magnitude of interobserver reliability when assessing canine USG via refractometry could impact clinical judgment. USG was determined in 38 dogs by 3 registered veterinary technicians (RVTs) using both an optical analog refractometer and a digital refractometer. Summary statistics were reported, interobserver reliability was assessed via intraclass correlation coefficient (ICC) analysis through a 2-way mixed-effects model, and agreement between RVT pairs was compared through Bland–Altman plots. The median analog refractometer USG measurement was 1.018 (range: 1.004–1.040) and for the digital refractometer was 1.0176 (1.0035–1.0357). The analog refractometer average measure ICC was 0.995 (95% CI: 0.992, 0.997; p

Urothelial carcinoma, also known as transitional cell carcinoma, is the most common primary bladder tumour in dogs, and can also involve the prostate gland. Cytology is a common diagnostic tool utilized for dogs with bladder or prostate gland lesions. The objectives of this retrospective study were to compare the sensitivity and specificity of cytologic evaluation for urothelial or prostatic carcinoma between two institutions with different cytology review protocols as well as determine if certain collection methods resulted in higher cytologic accuracy. A total of 298 cases met inclusion criteria. The overall sensitivity and specificity for institution 1 were 91.8% and 50%, respectively, compared to 31.1% and 97.4%, respectively, for institution 2. When the urine sample review protocol at institution 2 was matched to that of institution 1, sensitivity and specificity were more similar to institution 1 (71.2% and 88.9%, respectively). Our results show that the sensitivity and specificity of cytology are affected by screening and review protocols implemented by different institutions. The data also demonstrate that sensitivity and specificity vary by collection method. Diagnostic catheterization had the highest performance: of the 11 cases between two institutions, it had 100% sensitivity and specificity. In contrast, examination of urine sediment not collected via diagnostic catheterization had low sensitivity and specificity that varied greatly by institution. In summary, cytologic interpretation should be undertaken with consideration given to both processing and collection protocols.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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.

A 6-year-old, spayed female, mixed shorthair cat presented to the emergency service at The Ohio State University Veterinary Medical Center for evaluation of hypercalcemia, a right eye mass, and multiple intrathoracic and intra-abdominal masses. Cytologic evaluation of one of the abdominal masses revealed a uniform population of large, anaplastic mesenchymal cells found individually, in loose aggregates, and occasionally associated with pink, extracellular matrix. The cytology was consistent with a malignant mesenchymal neoplasm, with primary consideration given to fibrosarcoma and hemangiosarcoma. The cat was euthanized and histopathology confirmed disseminated fibrosarcoma. Fibrosarcoma comprises 12%-41% of feline cutaneous tumors and affects cats at a mean age of 9.6 years. Three manifestations of fibrosarcoma predominate in cats: spontaneous solitary fibrosarcoma, vaccine-induced/injection site fibrosarcoma, and oncogene-induced (FSV) fibrosarcoma. The history, signalment, and results from diagnostics performed did not support solitary fibrosarcoma or injection-induced sarcoma. Although some criteria fit with virally induced fibrosarcoma, such as age and the presence of multiple fibrosarcomas, the neoplastic population was negative for FeLV IHC. The presence of fibrosarcomas throughout the pleural and peritoneal cavity was most compatible with sarcomatosis and the distant metastasis of an unidentified primary neoplasm. To the authors' knowledge, this is the first reported case of sarcomatosis in a FeLV-negative cat.

Many recent advances in the evaluation of dogs with kidney disease have improved our diagnostic algorithms and have impacted our therapeutic strategies. Non-invasive techniques, such as urinary and serologic biomarker evaluation, can help a clinician diagnose and treat a patient that cannot undergo a renal biopsy for clinical or financial reasons. Some biomarkers might help localize the affected structure (glomerulus vs. tubule) and indicate the type or severity of injury present. Although more research is needed, studies indicate that some biomarkers (e.g. urine protein to creatinine ratio and urinary immunoglobulins) can be useful in predicting adverse outcomes. Importantly, the sensitivity and specificity of biomarkers for renal injury should be established and clinicians need to understand the limitations of these assays. If a renal biopsy is performed, then it should be evaluated by a specialty diagnostic service with expertise in nephropathology. A panel of special stains, immunofluorescence for the detection of immunoglobulins and complement factors, and transmission electron microscopy can be routinely employed in cases of glomerular disease. These advanced diagnostics can be used to detect immune deposits in order to definitively diagnose immune complex mediated glomerular disease. Integrating the results of biomarker assays and comprehensive renal biopsy evaluation, the clinician can make informed therapeutic decisions, such as whether or not to immunosuppress a patient.

Background Urine protein loss is common in dogs with chronic kidney disease (CKD). Hypothesis/Objectives To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD. Animals One hunderd and eighty dogs with naturally occurring kidney disease. Methods Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. Results Fractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex-mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM_FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM_FE: P = .008; TEM: P = .017). Conclusions and Clinical Importance Novel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival.

Dogs with X-linked hereditary nephropathy (XLHN) have a glomerular basement membrane defect that leads to progressive juvenile-onset renal failure. Their disease is analogous to Alport syndrome in humans, and they also serve as a good model of progressive chronic kidney disease (CKD). However, the gene expression profile that affects progression in this disease has only been partially characterized. To help fill this gap, we used RNA sequencing to identify differentially expressed genes (DEGs), over-represented pathways, and upstream regulators that contribute to kidney disease progression. Total RNA from kidney biopsies was isolated at 3 clinical time points from 3 males with rapidly-progressing CKD, 3 males with slowly-progressing CKD, and 2 age-matched controls. We identified 70 DEGs by comparing rapid and slow groups at specific time points. Based on time course analysis, 1,947 DEGs were identified over the 3 time points revealing upregulation of inflammatory pathways: integrin signaling, T cell activation, and chemokine and cytokine signaling pathways. T cell infiltration was verified by immunohistochemistry. TGF-β1 was identified as the primary upstream regulator. These results provide new insights into the underlying molecular mechanisms of disease progression in XLHN, and the identified DEGs can be potential biomarkers and therapeutic targets translatable to all CKDs.

A 10 yr old domestic longhair presented with a 2.5 mo history of recurrent hematuria. Abdominal ultrasound examination demonstrated a thickened urinary bladder, abdominal lymphadenopathy, and a thickened and rounded spleen. Cytologic examination of fine-needle aspirate samples revealed Histoplasma capsulatum organisms in the urinary bladder wall and spleen. The cat was treated with itraconazole (10 mg/kg per os q 24 hr for 2.5 wk). The cat was euthanized after 19 days of treatment because of lack of improvement. To the authors’ knowledge, this is the first documented case of feline disseminated histoplasmosis diagnosed in the urinary bladder wall.