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

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          Abstract

          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.

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          Most cited references32

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          Structural and Functional Changes With the Aging Kidney.

          Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.
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            Chronic enteropathies in dogs: evaluation of risk factors for negative outcome.

            Certain variables that are routinely measured during the diagnostic evaluation of dogs with chronic enteropathies will be predictive for outcome and a new clinical disease activity index incorporating these variables can be applied to predict outcome of disease. Seventy dogs were entered into a sequential treatment trial with elimination diet (FR, food-responsive group) followed by immunosuppressive treatment with steroids if no response was seen with the dietary trial alone (ST, steroid-treatment group). A 3rd group consisted of dogs with panhypoproteinemia and ascites (PLE, protein-losing enteropathy) that were treated with immunosuppressive doses of steroids. Three years of follow-up information was available for all dogs. Clinicopathologic variables were tested for their ability to predict negative outcome, defined as euthanasia due to refractoriness to treatment. Different scoring systems including different combinations of these variables were evaluated using receiver operating characteristic (ROC) curves. Thirteen of 70 (18%) dogs were euthanized because of intractable disease. Univariate analysis identified a high clinical activity index, high endoscopic score in the duodenum, hypocobalaminemia (<200 ng/L) and hypoalbuminemia (<20 g/L) as risk factors for negative outcome. Based on the factors identified by logistic regression and ROC curve analysis, a new clinical scoring index (CCECAI) was defined that predicts negative outcome in dogs suffering from chronic enteropathies.
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              Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

              FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among these FSGS types, classification of patients is often challenging. This review summarizes the clinical and histologic features, including the onset and severity of proteinuria as well as the presence of nephrotic syndrome, that may aid in identifying the specific FSGS subtype. The FSGS lesion is characterized by segmental sclerosis and must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features are pathognomonic for a particular FSGS subcategory. The characteristics of podocyte foot process effacement on electron microscopy, while helpful in discriminating between primary and maladaptive FSGS, may be of little utility in detecting genetic forms of FSGS. When FSGS cannot be classified by clinicopathologic assessment, genetic analysis should be offered. Next generation DNA sequencing enables cost-effective screening of multiple genes simultaneously, but determining the pathogenicity of a detected genetic variant may be challenging. A more systematic evaluation of patients, as suggested herein, will likely improve therapeutic outcomes and the design of future trials in FSGS.
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                Author and article information

                Contributors
                quimby.19@osu.edu
                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley & Sons, Inc. (Hoboken, USA )
                0891-6640
                1939-1676
                07 July 2020
                September 2020
                : 34
                : 5 ( doiID: 10.1111/jvim.v34.5 )
                : 1948-1956
                Affiliations
                [ 1 ] Department of Veterinary Clinical Sciences, College of Veterinary Medicine The Ohio State University Columbus Ohio USA
                [ 2 ] Department of Veterinary Biosciences, College of Veterinary Medicine The Ohio State University Columbus Ohio USA
                [ 3 ] International Veterinary Renal Pathology Service (IVRPS), Combined Service at The Ohio State University, Columbus, Ohio and Texas A&M College Station Texas USA
                Author notes
                [*] [* ] Correspondence

                Jessica M. Quimby, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH.

                Email: quimby.19@ 123456osu.edu

                Author information
                https://orcid.org/0000-0002-1388-0452
                Article
                JVIM15837
                10.1111/jvim.15837
                7517845
                33463760
                2a3bb2fd-d993-4964-b4e5-375e822ae5f5
                © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 March 2020
                : 12 June 2020
                : 13 June 2020
                Page count
                Figures: 2, Tables: 2, Pages: 9, Words: 7025
                Funding
                Funded by: Comparative Pathology and Mouse Phenotyping Shared Resource, Department of Veterinary Biosciences and the Comprehensive Cancer Center, the Ohio State University, Columbus OH
                Award ID: P30 CA016058
                Funded by: World Small Animal Veterinary Association (WSAVA)
                Award ID: N/A
                Categories
                Standard Article
                SMALL ANIMAL
                Standard Articles
                Nephrology/Urology
                Custom metadata
                2.0
                September 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:25.09.2020

                Veterinary medicine
                global glomerulosclerosis,glomerular disease,nonimmune complex glomerulopathy,podocyte,protein losing nephropathy,proteinuria,renal biopsy

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