title: Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss.
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.
authors.affiliation: Institut de Transplantation Et de Recherche en Transplantation, ITERT, CHU Nantes, RTRS «Centaure», France; LabEx Transplantex Nantes and Inserm U1064 (Immunointervention dans les Allo et Xénotransplantation), Nantes, France; Nantes University, Centre d'Investigation Clinique biothérapie, Nantes, France.
authors.forename: M
authors.initials: M
authors.lastname: Giral
authors.forename: Y
authors.initials: Y
authors.lastname: Foucher
authors.forename: A
authors.initials: A
authors.lastname: Dufay
authors.forename: J P
authors.initials: JP
authors.lastname: Duong Van Huyen
authors.forename: K
authors.initials: K
authors.lastname: Renaudin
authors.forename: A
authors.initials: A
authors.lastname: Moreau
authors.forename: A
authors.initials: A
authors.lastname: Philippe
authors.forename: B
authors.initials: B
authors.lastname: Hegner
authors.forename: R
authors.initials: R
authors.lastname: Dechend
authors.forename: H
authors.initials: H
authors.lastname: Heidecke
authors.forename: S
authors.initials: S
authors.lastname: Brouard
authors.forename: A
authors.initials: A
authors.lastname: Cesbron
authors.forename: S
authors.initials: S
authors.lastname: Castagnet
authors.forename: A
authors.initials: A
authors.lastname: Devys
authors.forename: J P
authors.initials: JP
authors.lastname: Soulillou
authors.forename: D
authors.initials: D
authors.lastname: Dragun
mesh_terms: D000208:Acute Disease; D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D044140:Receptor, Angiotensin, Type 1
keywords: Acute allograft rejection; allosensitization; angiotensin II receptors; antibody mediated rejection; pretransplant; survival