Reports have associated non‐HLA antibodies, specifically those against angiotensin II type‐1 receptor (AT1R), with antibody‐mediated kidney graft rejection. However, association of anti‐AT1R with graft failure had not been demonstrated. We tested anti‐AT1R and donor‐specific HLA antibodies (DSA) in pre‐ and posttransplant sera from 351 consecutive kidney recipients: 134 with biopsy‐proven rejection and/or lesions (abnormal biopsy group [ABG]) and 217 control group (CG) patients. The ABG's rate of anti‐AT1R was significantly higher than the CG's (18% vs. 6%, p < 0.001). Moreover, 79% of ABG patients with anti‐AT1R lost their grafts (vs. 0%, CG), anti‐AT1R levels in 58% of those failed grafts increasing posttransplant. With anti‐AT1R detectable before DSA, time to graft failure was 31 months—but 63 months with DSA detectable before anti‐AT1R. Patients with both anti‐AT1R and DSA had lower graft survival than those with DSA alone (log‐rank p = 0.007). Multivariate analysis showed that de novo anti‐AT1R was an independent predictor of graft failure in the ABG, alone (HR: 6.6), and in the entire population (HR: 5.4). In conclusion, this study found significant association of anti‐AT1R with graft failure. Further study is needed to establish causality between anti‐AT1R and graft failure and, thus, the importance of routine anti‐AT1R monitoring and therapeutic targeting.

These data indicate that proteasome inhibitors plus plasmapheresis results in prolonged reduction of HLA antibodies while leaving protective immunity intact.

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The Terasaki Institute for Biomedical Innovation is an independent non-profit organization and uses an integrative approach to innovate personalized health. The Institute draws on its scientific, entrepreneurial, and engineering skill set to transform ideas into clinically applicable technologies.

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