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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.

  • Author(s): Mai, Hoa Le
  • Treilhaud, Michèle
  • Ben-Arye, Shani Leviatan
  • Yu, Hai
  • Perreault, Hélène
  • Ang, Evelyn
  • Trébern-Launay, Katy
  • Laurent, Julie
  • Malard-Castagnet, Stéphanie
  • Cesbron, Anne
  • Nguyen, Thi Van Ha
  • Brouard, Sophie
  • Rostaing, Lionel
  • Houssel-Debry, Pauline
  • Legendre, Christophe
  • Girerd, Sophie
  • Kessler, Michèle
  • Morelon, Emmanuel
  • Sicard, Antoine
  • Garrigue, Valérie
  • Karam, Georges
  • Chen, Xi
  • Giral, Magali
  • Padler-Karavani, Vered
  • Soulillou, Jean Paul
  • et al.
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.

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