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Transplant Direct. 2018 Mar 20;4(4):e357. doi: 10.1097/TXD.0000000000000772. eCollection 2018 Apr.

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

Author information

1
Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
2
Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
3
Unité de Transplantation Thoracique, CHU Nantes, Nantes, France.
4
Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
5
Department of Chemistry, University of California-Davis, Davis, CA.
6
Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada.
7
Methodomics, Toulouse, France.
8
Laboratoire d'Histocompatibilité et d'Immunogénétique, Etablissement Français du Sang (EFS), CHU Nantes, Nantes, France.
9
Département de Néphrologie et Transplantation d'Organes, CHU Toulouse, Toulouse, France.
10
Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, France.
11
Service de Néphrologie et de Transplantation, Hôpital Necker, Université Paris Descartes, Paris, France.
12
Service de Néphrologie et Transplantation Rénale, CHU Nancy, Vandoeuvre-les-Nancy, France.
13
Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
14
Service de Néphrologie-Transplantation, Hôpital Lapeyronie, CHU Montpellier, France.

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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