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D. Dobi, Zs . Bodó, É. Kemény, K. Boda a , P. Szenohradszky b , E. Szederkényi b , B. Iványi

Kidney allografts with biopsy features of chronic mixed rejection reflect poorer survival than those with pure chronic antibody-mediated rejection. D. Dobi, Zs . Bodó, É. Kemény, K. Boda a , P. Szenohradszky b , E. Szederkényi b , B. Iványi

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D. Dobi, Zs . Bodó, É. Kemény, K. Boda a , P. Szenohradszky b , E. Szederkényi b , B. Iványi

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  1. Kidney allografts with biopsy features of chronic mixed rejection reflect poorer survival than those with pure chronic antibody-mediated rejection D. Dobi, Zs. Bodó, É. Kemény, K. Bodaa, P. Szenohradszkyb, E. Szederkényib, B. Iványi Departments of Pathology, Medical Physics and InformaticsaandSurgeryb University of Szeged, Szeged, Hungary

  2. Introduction In late dysfunctional kidney allograft biopsies three rejection phenotypes can be observed: • chronic antibody-mediated rejection (AMR) • acute T-cell-mediated rejection (TMR) • chronic active TMR

  3. Chronic AMR: transplant glomerulopathy and/or transplant capillaropathy cg ptcml

  4. Acute TMR: interstitialinfiltrates and tubulitis (interstitialrejection, ISR) withorwithoutintimalarteritis

  5. Chronicactive TMR: mononuclearsinintimalfibrosis (cvmo)

  6. Frequency: chronic AMR > acute TMR; chronicactiveTMR is exceptional • Chronic AMR and TMR mayconcur, termed chronic mixed rejection (CMR)

  7. Objectives Toanalyze • thehistologicalpatterns of chronic mixed rejection (CMR) • theclinicopathologicalrelevance of thedifferentpatternsof CMR

  8. Material and methods • From 2001 to 2011, 61 biopsies displayed thehistologicalfeatures of chronic AMR (cg and/orptcml± C4d-positivity) • Luminexdatawerenotavaible • Re-evaluationaccordingtotheBanffscheme (v, g, i, t, ptc, cg, ci,ct, ah) plus • Scoring of chronicarterialchanges: mononuclearsinintimalfibrosis (cvmo), intimalfibrosis (cvIF), intimalfibroelastosis (cvIFE); and tubular HLA-DR and ptcml

  9. Staining of chronic active arteritis (cvmo) cases with CD3 and CD68 in adjacent sections • Two groups for clinicopathological analysis: purely CAMR vs CMR • Statistics: Spearman’s correlation, hierarchical cluster analysis, Kaplan-Meier estimator, Cox regression

  10. Results: main clinicaldata

  11. CD3 Features of chronicactivearteritis Severeluminalnarrowing (medianscore 3), mononuclearsscatteredthroughoutthefibroticintima, T-cellpredominance CD68 PAS

  12. Significant (p<0.05) and positiveSpearmancorrelationcoefficientsbetweenBanffscoresandchronicarterialchanges

  13. Hierarchicalclusteranalysis cvIF cvmo cvIFE

  14. MeaneGFRvaluesinpurely CAMR and CMR

  15. Postbiopsytherapy

  16. Mean graft survival in purely CAMR and CMR groups 50vs22months Purely CAMR CMR p=0.011

  17. MultivariableCoxregression of morphologicalvariables cvmo ptc HLA-DR t i g C4d cvIF cg ptcml CNI-tox. ct ci ah cvIFE

  18. Discussion • CMR wasfrequentinour series (43%) • Chronic active arteritis appeared to beT-cell-related • T-cellpredominancein 14/16 cases • Clusteredwith TMR lesions C. Lefaucheur et al. Antibody-mediatedvascularrejection of kidneyallografts: a population-basedstudy. Lancet 2013; 381: 313-319.

  19. CMR wascharacterizedbypoorerallograftsurvival and more reducedallograftfunctionthanpurelychronic AMR ifchronicactivearteritiswas part of the TMR component • The immunohistochemical profiling of chronicactivearteritis is recommended

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