Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation
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 estab...
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Format: | Article |
Language: | English |
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Wolters Kluwer
2018-04-01
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Series: | Transplantation Direct |
Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000000772 |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Hoa Le Mai, PhD Michèle Treilhaud, MD Shani Leviatan Ben-Arye, PhD Hai Yu, PhD Hélène Perreault, PhD Evelyn Ang, PhD Katy Trébern-Launay, PhD Julie Laurent, PhD Stéphanie Malard-Castagnet, PhD Anne Cesbron, MD Thi Van Ha Nguyen, PhD Sophie Brouard, PhD Lionel Rostaing, MD Pauline Houssel-Debry, MD Christophe Legendre, MD Sophie Girerd, MD Michèle Kessler, MD Emmanuel Morelon, MD Antoine Sicard, MD Valérie Garrigue, MD Georges Karam, MD Xi Chen, PhD Magali Giral, MD Vered Padler-Karavani, PhD Jean Paul Soulillou, MD |
spellingShingle |
Hoa Le Mai, PhD Michèle Treilhaud, MD Shani Leviatan Ben-Arye, PhD Hai Yu, PhD Hélène Perreault, PhD Evelyn Ang, PhD Katy Trébern-Launay, PhD Julie Laurent, PhD Stéphanie Malard-Castagnet, PhD Anne Cesbron, MD Thi Van Ha Nguyen, PhD Sophie Brouard, PhD Lionel Rostaing, MD Pauline Houssel-Debry, MD Christophe Legendre, MD Sophie Girerd, MD Michèle Kessler, MD Emmanuel Morelon, MD Antoine Sicard, MD Valérie Garrigue, MD Georges Karam, MD Xi Chen, PhD Magali Giral, MD Vered Padler-Karavani, PhD Jean Paul Soulillou, MD Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation Transplantation Direct |
author_facet |
Hoa Le Mai, PhD Michèle Treilhaud, MD Shani Leviatan Ben-Arye, PhD Hai Yu, PhD Hélène Perreault, PhD Evelyn Ang, PhD Katy Trébern-Launay, PhD Julie Laurent, PhD Stéphanie Malard-Castagnet, PhD Anne Cesbron, MD Thi Van Ha Nguyen, PhD Sophie Brouard, PhD Lionel Rostaing, MD Pauline Houssel-Debry, MD Christophe Legendre, MD Sophie Girerd, MD Michèle Kessler, MD Emmanuel Morelon, MD Antoine Sicard, MD Valérie Garrigue, MD Georges Karam, MD Xi Chen, PhD Magali Giral, MD Vered Padler-Karavani, PhD Jean Paul Soulillou, MD |
author_sort |
Hoa Le Mai, PhD |
title |
Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation |
title_short |
Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation |
title_full |
Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation |
title_fullStr |
Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation |
title_full_unstemmed |
Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation |
title_sort |
poor patient and graft outcome after induction treatment by antithymocyte globulin in recipients of a kidney graft after nonrenal organ transplantation |
publisher |
Wolters Kluwer |
series |
Transplantation Direct |
issn |
2373-8731 |
publishDate |
2018-04-01 |
description |
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. |
url |
http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000000772 |
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doaj-c100cca4bfe24f5f9ebdfabf66a148ab2020-11-24T23:24:29ZengWolters KluwerTransplantation Direct2373-87312018-04-0144e35710.1097/TXD.0000000000000772201804000-0004Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ TransplantationHoa Le Mai, PhD0Michèle Treilhaud, MD1Shani Leviatan Ben-Arye, PhD2Hai Yu, PhD3Hélène Perreault, PhD4Evelyn Ang, PhD5Katy Trébern-Launay, PhD6Julie Laurent, PhD7Stéphanie Malard-Castagnet, PhD8Anne Cesbron, MD9Thi Van Ha Nguyen, PhD10Sophie Brouard, PhD11Lionel Rostaing, MD12Pauline Houssel-Debry, MD13Christophe Legendre, MD14Sophie Girerd, MD15Michèle Kessler, MD16Emmanuel Morelon, MD17Antoine Sicard, MD18Valérie Garrigue, MD19Georges Karam, MD20Xi Chen, PhD21Magali Giral, MD22Vered Padler-Karavani, PhD23Jean Paul Soulillou, MD241 Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de 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.6 Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada.1 Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.7 Methodomics, Toulouse, France.8 Laboratoire d'Histocompatibilité et d'Immunogénétique, Etablissement Français du Sang (EFS), CHU Nantes, Nantes, France.8 Laboratoire d'Histocompatibilité et d'Immunogénétique, Etablissement Français du Sang (EFS), CHU Nantes, Nantes, France.1 Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.1 Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de 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.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.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.2 Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.5 Department of Chemistry, University of California-Davis, Davis, CA.1 Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.4 Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.1 Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.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.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000000772 |