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. 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

Hoa Le Mai  1   2 , Michèle Treilhaud  3 , Shani Leviatan Ben-Arye  4 , Hai Yu  5 , Hélène Perreault  6 , Evelyn Ang  6 , Katy Trébern-Launay  1   2 , Julie Laurent  7 , Stéphanie Malard-Castagnet  8 , Anne Cesbron  8 , Thi Van Ha Nguyen  1   2 , Sophie Brouard  1   2 , Lionel Rostaing  9 , Pauline Houssel-Debry  10 , Christophe Legendre  11 , Sophie Girerd  12 , Michèle Kessler  12 , Emmanuel Morelon  13 , Antoine Sicard  13 , Valérie Garrigue  14 , Georges Karam  2 , Xi Chen  5 , Magali Giral  1   2 , Vered Padler-Karavani  4 , Jean Paul Soulillou  1   2
Affiliations

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

Hoa Le Mai et al. Transplant Direct. .

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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Figures

FIGURE 1
FIGURE 1
Patient flowchart.
FIGURE 2
FIGURE 2
Kaplan-Meier estimate of graft survival (noncensored for death). ATG induction was associated with significantly lower kidney graft survival compared with anti-IL-2R induction (P = 0.0017, log-rank test).
See this image and copyright information in PMC

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