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Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation

Hoa-Le Mai 1, 2 Michèle Treilhaud 3 Shani Leviatan Ben-Arye 4 Hai Yu 5 Hélène Perreault 6 Evelyn Ang 6, 7 Katy Trebern-Launay 1, 2 Julie Laurent 8 Stephanie Malard-Castagnet 9 Anne Cesbron 9 Thi van Ha Nguyen 1, 2 Sophie Brouard 1, 2 Lionel Rostaing 10 Pauline Houssel-Debry 11 Christophe Legendre 12 Sophie Girerd 13 Michèle Kessler 13 Emmanuel Morelon 14, 15 Antoine Sicard 15, 14 Valérie Garrigue 16 Georges Karam 17 Xi Chen 5 Magali Giral 2, 1 Vered Padler-Karavani 4 Jean-Paul Soulillou 1, 2
Abstract : BACKGROUND: End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). METHODS: We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. RESULTS: We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti-IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti-N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. CONCLUSIONS: Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.
Keywords : CRTI Team4 Team2
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https://www.hal.inserm.fr/hal-01881120
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Submitted on : Tuesday, September 25, 2018 - 2:52:06 PM
Last modification on : Saturday, June 6, 2020 - 9:04:03 AM

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Hoa-Le Mai, Michèle Treilhaud, Shani Leviatan Ben-Arye, Hai Yu, Hélène Perreault, et al.. Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation. Transplantation Direct, Wolters Kluwer, 2018, pp.1. ⟨10.1097/TXD.0000000000000772⟩. ⟨hal-01881120⟩

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