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Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss |
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| Authors: | Y Foucher A Dufay J P D Van Huyen K Renaudin A Moreau A Philippe B Hegner R Dechend H Heidecke A Cesbron S Castagnet A Devys J P Soulillou D Dragun |
| Institution: | 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;5. Service d'Anatomo Pathologie, Nantes, France;6. Clinic for Nephrology and Intensive Care Medicine, Charité Universit?tsmedizin, Berlin, Germany;7. Experimental and Clinical Research Center, Max‐Delbrück Center for Molecular Medicine and Charité Universit?tsmedizin, Berlin, Germany;8. CellTrend, 14943 Luckenwalde, Germany;9. Etablissement Fran?ais du Sang, Nantes, France |
| 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: | Acute allograft rejection allosensitization angiotensin II receptors antibody mediated rejection pretransplant survival |