Renal Transplant Rejection and Tolerance
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  • 1 Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
  • 1

    Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, et al.: The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transplant 20: 23182331, 2020 PubMed

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  • 2

    Nankivell BJ, Shingde M, Keung KL, Fung CL, Borrows RJ, O’Connell PJ, et al.: The causes, significance and consequences of inflammatory fibrosis in kidney transplantation: The Banff i-IFTA lesion. Am J Transplant 18: 364376, 2018 PubMed

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  • 3

    Mannon RB, Matas AJ, Grande J, Leduc R, Connett J, Kasiske B, et al.; DeKAF Investigators: Inflammation in areas of tubular atrophy in kidney allograft biopsies: A potent predictor of allograft failure. Am J Transplant 10: 20662073, 2010 PubMed

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  • 4

    Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, 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 18: 293307, 2018 PubMed

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  • 5

    Nakagawa K, Tsuchimoto A, Ueki K, Matsukuma Y, Okabe Y, Masutani K, et al.; Japan Academic Consortium of Kidney Transplantation Investigators: Significance of revised criteria for chronic active T cell-mediated rejection in the 2017 Banff classification: Surveillance by 1-year protocol biopsies for kidney transplantation. Am J Transplant 21: 174185, 2021 PubMed

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  • 6

    Matas AJ, Helgeson ES, Gaston R, Cosio F, Mannon R, Kasiske BL, et al.: Inflammation in areas of fibrosis: The DeKAF prospective cohort. Am J Transplant 20: 25092521, 2020 PubMed

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  • 7

    Schinstock CA, Sapir-Pichhadze R, Naesens M, Batal I, Bagnasco S, Bow L, et al.: Banff survey on antibody-mediated rejection clinical practices in kidney transplantation: Diagnostic misinterpretation has potential therapeutic implications. Am J Transplant 19: 123131, 2019 PubMed

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  • 8

    Callemeyn J, Ameye H, Lerut E, Senev A, Coemans M, Van Loon E, et al.: Revisiting the changes in the Banff classification for antibody-mediated rejection after kidney transplantation. Am J Transplant 21: 24132423, 2021 PubMed

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  • 9

    Mengel M, Loupy A, Haas M, Roufosse C, Naesens M, Akalin E, et al.: Banff 2019 Meeting Report: Molecular diagnostics in solid organ transplantation-Consensus for the Banff Human Organ Transplant (B-HOT) gene panel and open source multicenter validation. Am J Transplant 20: 23052317, 2020 PubMed

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  • 10

    Clayton PA, McDonald SP, Russ GR, Chadban SJ: Long-term outcomes after acute rejection in kidney transplant recipients: An ANZDATA analysis. J Am Soc Nephrol 30: 16971707, 2019 PubMed

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  • 11

    Van Loon E, Senev A, Lerut E, Coemans M, Callemeyn J, Van Keer JM, et al.: Assessing the complex causes of kidney allograft loss. Transplantation 104: 25572566, 2020 PubMed

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  • 12

    Hoffman W, Mehta R, Jorgensen DR, Sood P, Randhawa P, Wu CM, et al.: The impact of early clinical and subclinical T cell-mediated rejection after kidney transplantation. Transplantation 103: 14571467, 2019 PubMed

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  • 13

    Gupta A, Broin PO, Bao Y, Pullman J, Kamal L, Ajaimy M, et al.: Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies. Kidney Int 89: 217225, 2016 PubMed

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  • 14

    Grafft CA, Cornell LD, Gloor JM, Cosio FG, Gandhi MJ, Dean PG, et al.: Antibody-mediated rejection following transplantation from an HLA-identical sibling. Nephrol Dial Transplant 25: 307310, 2010 PubMed

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  • 15

    Parajuli S, Redfield RR, Garg N, Aziz F, Mohamed M, Astor BC, et al.: Clinical significance of microvascular inflammation in the absence of anti-HLA DSA in kidney transplantation. Transplantation 103: 14681476, 2019 PubMed

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  • 16

    Sis B, Jhangri GS, Riopel J, Chang J, de Freitas DG, Hidalgo L, et al.: A new diagnostic algorithm for antibody-mediated microcirculation inflammation in kidney transplants. Am J Transplant 12: 11681179, 2012 PubMed

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  • 17

    Senev A, Coemans M, Lerut E, Van Sandt V, Daniëls L, Kuypers D, et al.: Histological picture of antibody-mediated rejection without donor-specific anti-HLA antibodies: Clinical presentation and implications for outcome. Am J Transplant 19: 763780, 2019 PubMed

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  • 18

    Senev A, Lerut E, Van Sandt V, Coemans M, Callemeyn J, Sprangers B, et al.: Specificity, strength, and evolution of pretransplant donor-specific HLA antibodies determine outcome after kidney transplantation. Am J Transplant 19: 31003113, 2019 PubMed

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  • 19

    Lefaucheur C, Louis K, Philippe A, Loupy A, Coates PT: The emerging field of non-human leukocyte antigen antibodies in transplant medicine and beyond. Kidney Int 100: 787798, 2021 PubMed

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  • 20

    Lefaucheur C, Viglietti D, Bouatou Y, Philippe A, Pievani D, Aubert O, et al.: Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients. Kidney Int 96: 189201, 2019 PubMed

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  • 21

    Davis S, Gralla J, Klem P, Stites E, Wiseman A, Cooper JE: Tacrolimus intrapatient variability, time in therapeutic range, and risk of de novo donor-specific antibodies. Transplantation 104: 881887, 2020 PubMed

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  • 22

    Gonzales HM, McGillicuddy JW, Rohan V, Chandler JL, Nadig SN, Dubay DA, et al.: A comprehensive review of the impact of tacrolimus intrapatient variability on clinical outcomes in kidney transplantation. Am J Transplant 20: 19691983, 2020 PubMed

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  • 23

    Schinstock CA, Dadhania DM, Everly MJ, Smith B, Gandhi M, Farkash E, et al.: Factors at de novo donor-specific antibody initial detection associated with allograft loss: A multicenter study. Transpl Int 32: 502515, 2019 PubMed

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  • 24

    Schinstock CA, Cosio F, Cheungpasitporn W, Dadhania DM, Everly MJ, Samaniego-Picota MD, et al.: The value of protocol biopsies to identify patients with de novo donor-specific antibody at high risk for allograft loss. Am J Transplant 17: 15741584, 2017 PubMed

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  • 25

    Nevins TE, Nickerson PW, Dew MA: Understanding medication nonadherence after kidney transplant. J Am Soc Nephrol 28: 22902301, 2017 PubMed

  • 26

    Lim WH, Chapman JR, Coates PT, Lewis JR, Russ GR, Watson N, et al.: HLA-DQ mismatches and rejection in kidney transplant recipients. Clin J Am Soc Nephrol 11: 875883, 2016 PubMed

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  • 27

    DeVos JM, Gaber AO, Knight RJ, Land GA, Suki WN, Gaber LW, et al.: Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int 82: 598604, 2012 PubMed

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  • 28

    Duquesnoy RJ, Askar M: HLAMatchmaker: A molecularly based algorithm for histocompatibility determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP. Hum Immunol 68: 1225, 2007 PubMed

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  • 29

    Wiebe C, Kosmoliaptsis V, Pochinco D, Gibson IW, Ho J, Birk PE, et al.: HLA-DR/DQ molecular mismatch: A prognostic biomarker for primary alloimmunity. Am J Transplant 19: 17081719, 2019 PubMed

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  • 30

    Senev A, Coemans M, Lerut E, Van Sandt V, Kerkhofs J, Daniëls L, et al.: Eplet mismatch load and de novo occurrence of donor-specific anti-HLA antibodies, rejection, and graft failure after kidney transplantation: An observational cohort study. J Am Soc Nephrol 31: 21932204, 2020 PubMed

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  • 31

    Kramer C, Heidt S, Claas FHJ: Towards the identification of the relative immunogenicity of individual HLA antibody epitopes. Hum Immunol 80: 218220, 2019 PubMed

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  • 32

    Tambur AR, Kosmoliaptsis V, Claas FHJ, Mannon RB, Nickerson P, Naesens M: Significance of HLA-DQ in kidney transplantation: Time to reevaluate human leukocyte antigen-matching priorities to improve transplant outcomes? An expert review and recommendations. Kidney Int 100: 10121022, 2021 PubMed

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  • 33

    Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, et al.: Recommended treatment for antibody-mediated rejection after kidney transplantation: The 2019 Expert Consensus from the Transplantation Society Working Group. Transplantation 104: 911922, 2020 PubMed

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  • 34

    Bailly E, Ville S, Blancho G, Morelon E, Bamoulid J, Caillard S, et al.: An extension of the RITUX-ERAH study, multicenter randomized clinical trial comparing rituximab to placebo in acute antibody-mediated rejection after renal transplantation. Transpl Int 33: 786795, 2020 PubMed

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  • 35

    Sautenet B, Blancho G, Büchler M, Morelon E, Toupance O, Barrou B, et al.: One-year results of the effects of rituximab on acute antibody-mediated rejection in renal transplantation: RITUX ERAH, a multicenter double-blind randomized placebo-controlled trial. Transplantation 100: 391399, 2016 PubMed

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  • 36

    Marks WH, Mamode N, Montgomery RA, Stegall MD, Ratner LE, Cornell LD, et al.; C10-001 Study Group: Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial. Am J Transplant 19: 28762888, 2019 PubMed

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  • 37

    Glotz D, Russ G, Rostaing L, Legendre C, Tufveson G, Chadban S, et al.; C10-002 Study Group: Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies. Am J Transplant 19: 28652875, 2019 PubMed

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  • 38

    Schinstock CA, Bentall AJ, Smith BH, Cornell LD, Everly M, Gandhi MJ, et al.: Long-term outcomes of eculizumab-treated positive crossmatch recipients: Allograft survival, histologic findings, and natural history of the donor-specific antibodies. Am J Transplant 19: 16711683, 2019 PubMed

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  • 39

    Tan EK, Bentall A, Dean PG, Shaheen MF, Stegall MD, Schinstock CA: Use of eculizumab for active antibody-mediated rejection that occurs early post-kidney transplantation: A consecutive series of 15 cases. Transplantation 103: 23972404, 2019 PubMed

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  • 40

    Montgomery RA, Orandi BJ, Racusen L, Jackson AM, Garonzik-Wang JM, Shah T, et al.: Plasma-derived C1 esterase inhibitor for acute antibody-mediated rejection following kidney transplantation: Results of a randomized double-blind placebo-controlled pilot study. Am J Transplant 16: 34683478, 2016 PubMed

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  • 41

    Viglietti D, Gosset C, Loupy A, Deville L, Verine J, Zeevi A, et al.: C1 inhibitor in acute antibody-mediated rejection nonresponsive to conventional therapy in kidney transplant recipients: A pilot study. Am J Transplant 16: 15961603, 2016 PubMed

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  • 42

    Doberer K, Kläger J, Gualdoni GA, Mayer KA, Eskandary F, Farkash EA, et al.: CD38 antibody daratumumab for the treatment of chronic active antibody-mediated kidney allograft rejection. Transplantation 105: 451457, 2021 PubMed

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  • 43

    Jain D, Rajab A, Young JS, Yin D, Nadasdy T, Chong AS, et al.: Reversing donor-specific antibody responses and antibody-mediated rejection with bortezomib and belatacept in mice and kidney transplant recipients. Am J Transplant 20: 26752685, 2020 PubMed

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  • 44

    Jordan SC, Legendre C, Desai NM, Lorant T, Bengtsson M, Lonze BE, et al.: Imlifidase desensitization in crossmatch-positive, highly sensitized kidney transplant recipients: Results of an international phase 2 trial (Highdes). Transplantation 105: 18081817, 2021 PubMed

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  • 45

    Jordan SC, Choi J, Kim I, Wu G, Toyoda M, Shin B, et al.: Interleukin-6, A cytokine critical to mediation of inflammation, autoimmunity and allograft rejection: Therapeutic implications of IL-6 receptor blockade. Transplantation 101: 3244, 2017 PubMed

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  • 46

    Shin BH, Everly MJ, Zhang H, Choi J, Vo A, Zhang X, et al.: Impact of tocilizumab (anti-IL-6R) treatment on immunoglobulins and anti-HLA antibodies in kidney transplant patients with chronic antibody-mediated rejection. Transplantation 104: 856863, 2020 PubMed

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  • 47

    Pottebaum AA, Venkatachalam K, Liu C, Brennan DC, Murad H, Malone AF, et al.: Efficacy and safety of tocilizumab in the treatment of acute active antibody-mediated rejection in kidney transplant recipients. Transplant Direct 6: e543, 2020 PubMed

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  • 48

    Choi J, Aubert O, Vo A, Loupy A, Haas M, Puliyanda D, et al.: Assessment of tocilizumab (anti-interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant glomerulopathy in HLA-sensitized renal allograft recipients. Am J Transplant 17: 23812389, 2017 PubMed

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  • 49

    Massat M, Congy-Jolivet N, Hebral AL, Esposito L, Marion O, Delas A, et al.; Toulouse Acquired Immune Deficiency, Infection (TAIDI) Study Group: Do anti-IL-6R blockers have a beneficial effect in the treatment of antibody-mediated rejection resistant to standard therapy after kidney transplantation? Am J Transplant 21: 16411649, 2021 PubMed

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  • 50

    Eskandary F, Dürr M, Budde K, Doberer K, Reindl-Schwaighofer R, Waiser J, et al.: Clazakizumab in late antibody-mediated rejection: Study protocol of a randomized controlled pilot trial. Trials 20: 37, 2019 PubMed

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  • 51

    Doberer K, Duerr M, Halloran PF, Eskandary F, Budde K, Regele H, et al.: A randomized clinical trial of anti-IL-6 antibody clazakizumab in late antibody-mediated kidney transplant rejection. J Am Soc Nephrol 32: 708722, 2021 PubMed

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  • 52

    CSL Behring: Clazakizumab for the Treatment of Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients (IMAGINE), 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03744910. Accessed August 15, 2021

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    Rickert CG, Markmann JF: Current state of organ transplant tolerance. Curr Opin Organ Transplant 24: 441450, 2019 PubMed

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    Newell KA, Adams AB, Turka LA: Biomarkers of operational tolerance following kidney transplantation: The immune tolerance network studies of spontaneously tolerant kidney transplant recipients. Hum Immunol 79: 380387, 2018 PubMed

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  • 56

    Sagoo P, Perucha E, Sawitzki B, Tomiuk S, Stephens DA, Miqueu P, et al.: Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans. J Clin Invest 120: 18481861, 2010 PubMed

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  • 57

    Busque S, Scandling JD, Lowsky R, Shizuru J, Jensen K, Waters J, et al.: Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal. Sci Transl Med 12: eaax8863, 2020 PubMed

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  • 58

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  • 59

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  • 60

    Issa F, Strober S, Leventhal JR, Kawai T, Kaufman DB, Levitsky J, et al.: The Fourth International Workshop on Clinical Transplant Tolerance. Am J Transplant 21: 2131, 2021 PubMed

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  • 61

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