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      What is the best way to measure renal fibrosis?: A pathologist's perspective

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          Abstract

          Interstitial fibrosis is a hallmark structural correlate of progressive and chronic kidney disease. There remain many uncertainties about how to best measure interstitial fibrosis both in research settings and in evaluations of renal biopsies performed for management of individual patients. Areas of uncertainty include determination of the composition of the matrix in a fibrotic parenchyma, the definition of how the interstitium is involved by fibrosing injuries, the choice of histologic stains for evaluation of renal fibrosis, and the reproducibility and robustness of measures currently employed by pathologists, both with and without the assistance of computerized imaging and assessments. In this review, we address some of these issues while citing the key studies that illustrate these difficulties. We point to future approaches that may allow a more accurate and meaningful assessment of renal interstitial fibrosis.

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          Pathologic classification of diabetic nephropathy.

          Although pathologic classifications exist for several renal diseases, including IgA nephropathy, focal segmental glomerulosclerosis, and lupus nephritis, a uniform classification for diabetic nephropathy is lacking. Our aim, commissioned by the Research Committee of the Renal Pathology Society, was to develop a consensus classification combining type1 and type 2 diabetic nephropathies. Such a classification should discriminate lesions by various degrees of severity that would be easy to use internationally in clinical practice. We divide diabetic nephropathy into four hierarchical glomerular lesions with a separate evaluation for degrees of interstitial and vascular involvement. Biopsies diagnosed as diabetic nephropathy are classified as follows: Class I, glomerular basement membrane thickening: isolated glomerular basement membrane thickening and only mild, nonspecific changes by light microscopy that do not meet the criteria of classes II through IV. Class II, mesangial expansion, mild (IIa) or severe (IIb): glomeruli classified as mild or severe mesangial expansion but without nodular sclerosis (Kimmelstiel-Wilson lesions) or global glomerulosclerosis in more than 50% of glomeruli. Class III, nodular sclerosis (Kimmelstiel-Wilson lesions): at least one glomerulus with nodular increase in mesangial matrix (Kimmelstiel-Wilson) without changes described in class IV. Class IV, advanced diabetic glomerulosclerosis: more than 50% global glomerulosclerosis with other clinical or pathologic evidence that sclerosis is attributable to diabetic nephropathy. A good interobserver reproducibility for the four classes of DN was shown (intraclass correlation coefficient = 0.84) in a test of this classification.
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            Fibrotic disease and the T(H)1/T(H)2 paradigm.

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              The Banff 97 working classification of renal allograft pathology.

              Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions.
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                Author and article information

                Journal
                Kidney Int Suppl (2011)
                Kidney Int Suppl (2011)
                Kidney International Supplements
                Nature Publishing Group
                2157-1724
                2157-1716
                November 2014
                31 October 2014
                : 4
                : 1
                : 9-15
                Affiliations
                [1 ]Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia, USA
                [2 ]Department of Pathology, University of Washington , Seattle, Washington, USA
                Author notes
                [* ]Department of Pathology, University of Washington , Medical Center Box 356100, Seattle, Washington 98195-6100, USA. E-mail: calp@ 123456uw.edu
                Article
                kisup20143
                10.1038/kisup.2014.3
                4536972
                6040e3a5-539f-4dd4-9cd1-65d3b4c2aad7
                Copyright © 2014 International Society of Nephrology
                History
                Categories
                Mini Review

                collagen,fibrosis,interstitial fibrosis,morphometry,picrosirius red,trichrome stain

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