Preformed Angiotensin II Type-1 Receptor Antibodies Are Associated With Rejection After Kidney Transplantation: A...

Antibodies against angiotensin II type-1 receptors (AT1R) have been increasingly recognized in association with rejection and poor allograft outcomes. Our goal was to define the prevalence of preformed antibodies against AT1R and evaluate the association with renal allograft outcomes in a consecutive cohort of 150 transplant recipients. IgG antibodies against AT1R were measured by enzyme-linked immunosorbent assay using cryopreserved serum samples obtained for HLA testing at the time of transplantation. Results were categorized as negative if <10 U/mL (44%), intermediate from 10 to 17 U/mL (38%), or strongly positive if >17 U/mL (18%). The presence of AT1R antibodies was inversely associated with age, dialysis status, and diabetes. We found a strong association between the presence of AT1R antibodies and acute cellular rejection using multivariate analyses, odds ratio 3.86 (95% CI, 1.03-14.47) for intermediate titers and 9.99 (95% CI, 2.6-38.4) for strongly positive titers. There was no association with HLA sensitization or C4d-positive antibody-mediated rejection. We did not observe a significant association with graft failure, allograft function, or proteinuria. Preformed AT1R antibodies are prevalent and highly associated with acute cellular rejection early after transplant, independent of anti-HLA antibodies. The presence of AT1R antibodies correlates with recipient characteristics that may denote stronger immune responses. Future studies are needed to evaluate the mechanism and causative effect of AT1R antibodies.