Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss

Authors

  • M. Giral,

    1. Institut de Transplantation Et de Recherche en Transplantation, ITERT, CHU Nantes, RTRS «Centaure», France
    2. LabEx Transplantex Nantes and Inserm U1064 (Immunointervention dans les Allo et Xénotransplantation), Nantes, France
    3. Nantes University, Centre d'Investigation Clinique biothérapie, Nantes, France
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    • Both authors contributed equally.
  • Y. Foucher,

    1. Institut de Transplantation Et de Recherche en Transplantation, ITERT, CHU Nantes, RTRS «Centaure», France
    2. LabEx Transplantex Nantes and Inserm U1064 (Immunointervention dans les Allo et Xénotransplantation), Nantes, France
    3. Nantes University, Centre d'Investigation Clinique biothérapie, Nantes, France
    4. EA 4275—Biostatistics, Clinical Reasearch and Pharmaco-Epidemiology. Nantes University, Nantes, France
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  • A. Dufay,

    1. Institut de Transplantation Et de Recherche en Transplantation, ITERT, CHU Nantes, RTRS «Centaure», France
    2. LabEx Transplantex Nantes and Inserm U1064 (Immunointervention dans les Allo et Xénotransplantation), Nantes, France
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  • J. P. D. Van Huyen,

    Corresponding author
    1. Institut de Transplantation Et de Recherche en Transplantation, ITERT, CHU Nantes, RTRS «Centaure», France
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  • K. Renaudin,

    1. LabEx Transplantex Nantes and Inserm U1064 (Immunointervention dans les Allo et Xénotransplantation), Nantes, France
    2. Service d'Anatomo Pathologie, Nantes, France
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  • A. Moreau,

    1. Service d'Anatomo Pathologie, Nantes, France
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  • A. Philippe,

    1. Clinic for Nephrology and Intensive Care Medicine, Charité Universitätsmedizin, Berlin, Germany
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  • B. Hegner,

    1. Clinic for Nephrology and Intensive Care Medicine, Charité Universitätsmedizin, Berlin, Germany
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  • R. Dechend,

    1. Experimental and Clinical Research Center, Max-Delbrück Center for Molecular Medicine and Charité Universitätsmedizin, Berlin, Germany
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  • H. Heidecke,

    1. CellTrend, 14943 Luckenwalde, Germany
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  • S. Brouard,

    1. Institut de Transplantation Et de Recherche en Transplantation, ITERT, CHU Nantes, RTRS «Centaure», France
    2. LabEx Transplantex Nantes and Inserm U1064 (Immunointervention dans les Allo et Xénotransplantation), Nantes, France
    3. Nantes University, Centre d'Investigation Clinique biothérapie, Nantes, France
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    • Both authors contributed equally.
  • A. Cesbron,

    1. Etablissement Français du Sang, Nantes, France
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  • S. Castagnet,

    1. Etablissement Français du Sang, Nantes, France
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  • A. Devys,

    1. Etablissement Français du Sang, Nantes, France
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  • J. P. Soulillou,

    1. Institut de Transplantation Et de Recherche en Transplantation, ITERT, CHU Nantes, RTRS «Centaure», France
    2. LabEx Transplantex Nantes and Inserm U1064 (Immunointervention dans les Allo et Xénotransplantation), Nantes, France
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  • D. Dragun

    1. Clinic for Nephrology and Intensive Care Medicine, Charité Universitätsmedizin, Berlin, Germany
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Abstract

The angiotensin II type 1 receptor (AT1R) is an emerging target of functional non-HLA antibodies (Ab). We examined the potential of determining the degree of presensitization against AT1R as a risk factor for graft survival and acute rejection (AR). The study included 599 kidney recipients between 1998 and 2007. Serum samples were analyzed in a blinded fashion for anti-AT1R antibodies (AT1R-Abs) using a quantitative solid-phase assay. A threshold of AT1R-Ab levels was statistically determined at 10 U based on the time to graft failure. An extended Cox model determined risk factors for occurrence of graft failure and a first AR episode. AT1R-Abs >10 U were detected in 283 patients (47.2%) before transplantation. Patients who had a level of AT1R-Abs >10 U had a 2.6-fold higher risk of graft failure from 3 years posttransplantation onwards (p = 0.0005) and a 1.9-fold higher risk of experiencing an AR episode within the first 4 months of transplantation (p = 0.0393). Antibody-mediated rejection (AMR) accounted for 1/3 of AR, whereby 71.4% of them were associated with >10 U of pretransplant AT1R-Abs. Pretransplant anti-AT1R-Abs are an independent risk factor for long-term graft loss in association with a higher risk of early AR episodes.

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