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

The angiotensin II type 1 receptor (AT(1)R) is an emerging target of functional non-HLA antibodies (Ab). We examined the potential of determining the degree of presensitization against AT(1)R 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-AT(1)R antibodies (AT(1)R-Abs) using a quantitative solid-phase assay. A threshold of AT(1)R-Ab levels was statistically determined at 10U based on the time to graft failure. An extended Cox model determined risk factors for occurrence of graft failure and a first AR episode. AT(1)R-Abs >10U were detected in 283 patients (47.2%) before transplantation. Patients who had a level of AT(1)R-Abs >10U 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 >10U of pretransplant AT(1)R-Abs. Pretransplant anti-AT(1)R-Abs are an independent risk factor for long-term graft loss in association with a higher risk of early AR episodes.