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

M. Giral 1, 2, 3, 4, 5 Y. Foucher 1, 2, 3, 4, 5, 6 A. Dufay 1, 2, 3, 4 J. van Huyen 2, 3 K. Renaudin 1, 4, 7 A. Moreau 7 A. Philippe 8 B. Hegner 8 R. Dechend 9 H. Heidecke 10 S. Brouard 1, 2, 3, 4, 5 A. Cesbron 11 S. Castagnet 11 A. Devys 11 Jean Soulillou 1, 2, 3, 4, * D. Dragun 8
* Corresponding author
1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 ITERT - Institut de Transplantation et de Recherche en Transplantation [CHU Nantes]
3 Réseau CENTAURE [Nantes]
4 LabEx TRANSPLANTEX [CHU de Nantes]
5 CIC biothérapies CBT 0503 [Nantes]
6 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé
7 Service d’Anatomopathologie [CHU Nantes]
8 Clinic for Nephrology and Intensive Care Medicine [Berlin, Germany]
9 Experimental and Clinical Research Center [Berlin, Germany]
10 CellTrend [Luckenwalde, Germany]
11 Etablissement Français du Sang [Nantes]
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.
Keywords : survival Acute allograft rejection allosensitization angiotensin II receptors antibody mediated rejection pretransplant
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INSERM | UNAM | UNIV-NANTES | CRTI

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M. Giral, Y. Foucher, A. Dufay, J. van Huyen, K. Renaudin, et al.. Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss. American Journal of Transplantation, Wiley, 2013, 13 (10), pp.2567-2576. ⟨10.1111/ajt.12397⟩. ⟨inserm-02165660⟩

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