TY - JOUR
T1 - Poor Patient and graft outcome after induction treatment by antithymocyte globulin in recipients of a kidney graft after nonrenal organ transplantation
AU - Mai, Hoa Le
AU - Treilhaud, Michèle
AU - Ben-Arye, Shani Leviatan
AU - Yu, Hai
AU - Perreault, Hélène
AU - Ang, Evelyn
AU - Trébern-Launay, Katy
AU - Laurent, Julie
AU - Malard-Castagnet, Stéphanie
AU - Cesbron, Anne
AU - Nguyen, Thi Van Ha
AU - Brouard, Sophie
AU - Rostaing, Lionel
AU - Houssel-Debry, Pauline
AU - Legendre, Christophe
AU - Girerd, Sophie
AU - Kessler, Michèle
AU - Morelon, Emmanuel
AU - Sicard, Antoine
AU - Garrigue, Valérie
AU - Karam, Georges
AU - Chen, Xi
AU - Giral, Magali
AU - Padler-Karavani, Vered
AU - Soulillou, Jean Paul
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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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U2 - 10.1097/TXD.0000000000000772
DO - 10.1097/TXD.0000000000000772
M3 - Article
AN - SCOPUS:85053681367
VL - 4
JO - Transplantation Direct
JF - Transplantation Direct
SN - 2373-8731
IS - 4
M1 - e357
ER -