Supplemental Digital Content - Lippincott Williams & Wilkins
Supplemental Digital ContentSDC 1, Glossary of termsAcute Tubular InjuryThere is no current definition of acute tubular injury endorsed by the Banff classification. Acute Tubular Injury In the Absence Of Any Other Apparent Cause is included as one of the criteria for histological evidence of acute tissue injury in the diagnosis of Active AMR.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (1) Diagnostic subcategories within include the following; C4d Staining Without Evidence of Rejection, Active AMR, Chronic Active AMR, Chronic AMR. AMR can coexist with additional diagnoses from Banff Diagnostic Categories 3-6.Adequacy of SpecimenSince Banff 1997PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SYWN1c2VuPC9BdXRob3I+PFllYXI+MTk5OTwvWWVhcj48
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ZE5vdGU+AG==
ADDIN EN.CITE.DATA (2) a biopsy has been considered adequate if it contains at least 10 or more glomeruli and at least 2 arteries; the threshold for a “minimal sample” is 7 glomeruli and 1 artery. It is also recommended that at least 2 separate cores containing cortex be obtained or that there be 2 separate areas of cortex in the same core.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb3VweTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (1) This can be used in conjunction with other Banff categories with the exception of Category 1 (Normal Biopsy Or Nonspecific Changes) or 4 (Acute TCMR Grade IA, IIA, IIB or III, Chronic active TCMR Grade IA, IB or II).C4dComplement component 4 fragment d (C4d) is a degradation product of complement component C4, which can bind covalently to the endothelial cell surface.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZWdlbGU8L0F1dGhvcj48WWVhcj4yMDAyPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (3) The clinical significance of these findings is different in grafts exposed to anti-blood group antibodies (ABO-incompatible allografts), in which isoagglutinin-mediated complement activation does not appear to be injurious to the graft and may represent accommodation. However, when caused by donor-specific antibodies against HLA or other antigens, it may indicate AMR activity. Based on the high specificity of C4d positivity, it is considered equivalent to the serological proof of donor-specific antibody (DSA) for a diagnosis of AMR, although it is still recommended to test for DSA.Banff Diagnostic CategoriesThis refers to the six consensus-based and empirically validated Banff Diagnostic Categories (1 to 6) for renal allograft biopsies.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (1) Diagnoses from different Banff Diagnostic Categories can be used if required in any combination other than Category 1, 3 and 4 which are mutually exclusive. Moreover, any diagnosis from Categories 2-6 excludes Banff Diagnostic Category 1 (Normal Biopsy or Nonspecific changes). Multiple diagnoses from a single Banff Diagnostic Category can only be made from Category 6.Banff Lesion ScoresBanff Lesion Scores are descriptive, consensus-based, standardised terms to grade important active and chronic histopathological findings in the different morphological compartments of the renal transplant. Although they are an integral part of the minimal dataset, they are by themselves not necessarily sufficient to determine Banff Diagnostic Categories. Chronic Allograft ArteriopathyChronic Allograft Arteriopathy is a feature of Chronic Active TCMR and Chronic Active AMR. It is defined as arterial intimal fibrosis with mononuclear cell infiltration in fibrosis and/or formation of neointima. The Banff Lesion Score cv is used to grade it, based on the extent of luminal occlusion in the most severely affected artery. Lack of prior biopsy-proven TCMR favours a diagnosis of Chronic Active AMR.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (1)CortexThe outer part of the renal parenchyma, beneath the capsule and peripheral from the medulla, including the columns of Bertin. It is characterised by the presence of glomeruli and arteries. ADDIN EN.CITE <EndNote><Cite><Author>Bonsib</Author><Year>2015</Year><RecNum>9117</RecNum><DisplayText>(<style face="italic">6</style>)</DisplayText><record><rec-number>9117</rec-number><foreign-keys><key app="EN" db-id="90tpszswbfs2f3evsw8vz9a52vrp9e2xa95e" timestamp="0">9117</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Bonsib, S. M.</author></authors><secondary-authors><author>Jennette, C. J.</author><author>Silva, F. G.</author><author>Olson, J. L.</author><author>D'Agati, V. D.</author></secondary-authors></contributors><titles><title>Renal Anatomy and Histology</title><secondary-title>Heptinstall's Pathology of the Kidney</secondary-title></titles><pages>1-66</pages><volume>1</volume><num-vols>2</num-vols><section>1</section><dates><year>2015</year></dates><pub-location>Philadelphia, PA, USA</pub-location><publisher>Lippincot Williams & Wilkins</publisher><isbn>978-1-4511-4411-6</isbn><urls></urls></record></Cite></EndNote>(6)Donor-specific Antibody (DSA)Circulating antibodies directed against donor human leukocyte antigen (HLA) class I and/or class II and/or non-HLA antigens. For the definition and technical details see the recent and forthcoming consensus recommendations by The Transplantation Society.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWl0PC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (1)GlomerulonephritisRecurrent or de novo glomerulonephritis can occur in renal transplant biopsies. The diagnosis is made by a combination of conventional histology, immunohistochemistry or immunofluorescence, electron microscopy and correlation with clinical data. It should be diagnosed under Banff Diagnostic Category 6, and can be used in combination with categories 2-5 and any other diagnosis from Category 6. The presence of glomerulonephritis precludes the use of Banff Lesion Score g as histologic evidence of acute tissue injury for the diagnosis of Active AMR and of Banff Lesion Score cg as evidence of chronic tissue injury in the diagnosis of Chronic Active or Chronic AMR.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (1)Haemorrhage, TubulointerstitialExtravasation of red blood cells into the tubulointerstitium. There is no special Banff Lesion Score for this lesion. Instead the lesion is noted as an asterisk “*” attached to Banff Lesion Score v (e.g. v0* or v3*). It shares this coding with Infarct.InfarctZone of tissue which is non-viable due to insufficient blood supply. It qualifies as “necrosis” listed in the supplement of Banff 2015 and since Banff 1997 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SYWN1c2VuPC9BdXRob3I+PFllYXI+MTk5OTwvWWVhcj48
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ADDIN EN.CITE.DATA (8)InfectionIn the presence of Infection (Table 5, Banff 2017) Banff Lesion Score g>0 greater is required when using moderate microvascular inflammation (sum of Banff g+ptc≥2) as a criterion from Criteria Group 3 (antibody interaction with tissue) for a diagnosis of Active AMR or Chronic Active AMR.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (1) I.e. Banff Lesion Score ptc2 with Banff Lesion Score g0 is insufficient for this criterion when disease caused by infection of the transplant is present.Interstitial fibrosisBanff Lesion Score ci for interstitial fibrosis was initially meant to describe the area fraction of fibrous tissue in the cortex only regardless of whether it represented fibrous tissue as the normal constituent of the renal cortex (considered to be 5%) or fibrous tissue within a cortical scar. Hence, a precise definition for individual patches of interstitial fibrosis in a scar has never been given. This purely morphometric approach runs counterintuitive to routine histopathological assessment for atrophic tubules separated by interstitial fibrosis in a tubulointerstitial scar. Guides for the assessment of Banff Lesion Score ci can be found in the main body of this manuscript.Microvascular Inflammation, ModerateMicrovascular inflammation is scored by calculating the sum of the two Banff Lesion Scores g and ptc. Microvascular inflammation is considered moderate with Banff Lesion Scores g + ptc ≥2. In the presence of Acute TCMR, Borderline Changes or Infection such as Pyelonephritis, Banff Lesion Score g must be equal or greater than 1 in this calculation to fulfil the criteria for moderate microvascular inflammation.Peritubular CapillaryOnly capillaries within the renal cortex are peritubular capillaries (PTCs) which can be used for scoring peritubular capillaritis as in Banff Lesion Score ptc. Capillaries next to lymphoid follicles must be disregarded to avoid confusion with lymphatic vessels. Banff Lesion Score C4d can be scored not only in PTCs but also in medullary vasa recta.Peritubular Capillary Basement Membrane MultilayeringSevere Peritubular Capillary Basement Membrane Multilayering (PTCML) is defined as “seven or more layers of basement membrane in one cortical peritubular capillary and five or more in two additional capillaries, avoiding portions cut tangentially“.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (1) Only Severe Peritubular Capillary Basement Membrane Multilayering is considered sufficient as one possible criterion for chronicity of AMR. This relative high threshold has been established because mild PTCML can be seen in other diseases like hypertension. In cases where electron microscopy (EM) is carried out in transplant biopsies, cortical peritubular capillary multilayering should be assessed and reported. The number of layers of basement membrane should be counted in the most affected PTC as well as in at least two additional PTCs. Tangentially cut PTC should be avoided. See also recommendations for performing EM cited from the Banff 2015 report under Banff Lesion Score cg for more detail.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb3VweTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (3)PyelonephritisInflammation of the transplant parenchyma caused by bacterial or fungal infection, usually ascending from the bladder. This falls within the remit of Banff Diagnostic Category 6. As an Infection, the presence of Pyelonephritis has important bearings on the diagnosis of Active AMR and Chronic Active AMR, as then Banff Lesion Score g must be equal or greater than 1 to fulfil the criteria for Microvascular inflammation, Moderate (Banff Lesion Score g + ptc ≥2).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWFzPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (9) Polyomavirus nephropathy is included in Banff Diagnostic Category 6 as BK-Virus Nephropathy.Scarred Cortical ParenchymaCharacterised by cortical tubular atrophy, usually but not always accompanied by interstitial fibrosis –see Tubular Atrophy. Banff Lesion Score i must not be scored in these areas, instead Banff Lesion Score i-IFTA is assessed in the areas.Subcapsular CortexThis term refers to areas immediately beneath the capsule, which may show areas of non-specific scarring or inflammation thought to be related to surgical ‘healing in’. ADDIN EN.CITE <EndNote><Cite><Author>Solez</Author><Year>1993</Year><RecNum>5850</RecNum><DisplayText>(<style face="italic">10</style>)</DisplayText><record><rec-number>5850</rec-number><foreign-keys><key app="EN" db-id="90tpszswbfs2f3evsw8vz9a52vrp9e2xa95e" timestamp="0">5850</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Solez, K.</author><author>Axelsen, R. A.</author><author>Benediktsson, H.</author><author>Burdick, J. F.</author><author>Cohen, A. H.</author><author>Colvin, R. B.</author><author>Croker, B. P.</author><author>Droz, D.</author><author>Dunnill, M. S.</author><author>Halloran, P. F.</author><author>et al.,</author></authors></contributors><auth-address>Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.</auth-address><titles><title>International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology</title><secondary-title>Kidney Int</secondary-title><alt-title>Kidney international</alt-title></titles><periodical><full-title>Kidney Int</full-title><abbr-1>Kidney international</abbr-1></periodical><alt-periodical><full-title>Kidney Int</full-title><abbr-1>Kidney international</abbr-1></alt-periodical><pages>411-22</pages><volume>44</volume><number>2</number><edition>1993/08/01</edition><keywords><keyword>Graft Rejection/*pathology</keyword><keyword>Humans</keyword><keyword>*International Cooperation</keyword><keyword>Kidney/*pathology</keyword><keyword>*Kidney Transplantation</keyword><keyword>Pathology/standards</keyword><keyword>Reference Standards</keyword><keyword>Terminology as Topic</keyword></keywords><dates><year>1993</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0085-2538 (Print)
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ADDIN EN.CITE.DATA (1)Transplant ArteriopathyTransplant Arteriopathy is defined as arterial fibrointimal thickening, also referred to as vascular fibrous intimal thickening, and is graded based on the extent of luminal occlusion in the most severely affected artery. Transplant arteriopathy is scored with the Banff Lesion Score cv. Features that suggest Chronic Active TCMR Grade II or Chronic Active AMR versus other causes such as conventional arteriosclerosis or hypertension are disruption of the elastica, inflammatory cells in the fibrotic intima, proliferation of myofibroblasts and/or foam cells in the expanded intima, formation of a neointima.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb3VweTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (13)Transplant GlomerulopathyTransplant glomerulopathy is defined as a Banff Lesion Score cg greater than 0, after the exclusion of chronic thrombotic microangiopathy, recurrent or de novo Glomerulonephritis. It is not synonymous to AMR, but is frequently associated with it.Tubular AtrophyModerately atrophic tubules are defined as tubules having a diameter <50% of that of unaffected or minimally affected tubules on the biopsy, with wrinkling and/or thickening of the tubular basement membrane.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SYWN1c2VuPC9BdXRob3I+PFllYXI+MTk5OTwvWWVhcj48
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ADDIN EN.CITE.DATA (1)References ADDIN EN.REFLIST 1.Haas M, Loupy A, Lefaucheur C et al. The Banff 2017 Kidney Meeting Report: Revised Diagnostic Criteria for Chronic Active T Cell-Mediated Rejection, Antibody-Mediated Rejection, and Prospects for Integrative Endpoints for Next-Generation Clinical Trials. Am J Transplant 20172.Racusen LC, Solez K, Colvin RB et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999;55(2):713-7233.Loupy A, Haas M, Solez K et al. The Banff 2015 Kidney meeting report: Current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant 2017;17(1):28-414.Haas M, Sis B, Racusen LC et al. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014;14(2):272-2835.Regele H, Bohmig GA, Habicht A et al. Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: a contribution of humoral immunity to chronic allograft rejection. J Am Soc Nephrol 2002;13(9):2371-23806.Bonsib SM. Renal Anatomy and Histology. In: Jennette CJ, Silva FG, Olson JL, et al., eds. Heptinstall's Pathology of the Kidney. Lippincot Williams & Wilkins: Philadelphia, PA, USA; 2015, 1-66.7.Tait BD, Susal C, Gebel HM et al. Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation 2013;95(1):19-478.Solez K, Colvin RB, Racusen LC et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008;8(4):753-7609.Nickeleit V, Singh HK, Randhawa P et al. The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations. J Am Soc Nephrol 201710.Solez K, Axelsen RA, Benediktsson H et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int 1993;44(2):411-42211.Solez K, Colvin RB, Racusen LC et al. Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). Am J Transplant 2007;7(3):518-52612.Noris M, Remuzzi G. Thrombotic microangiopathy after kidney transplantation. Am J Transplant 2010;10(7):1517-152313.Hill GS, Nochy D, Bruneval P et al. Donor-specific antibodies accelerate arteriosclerosis after kidney transplantation. J Am Soc Nephrol 2011;22(5):975-983 ................
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