M. Taniguchi, L.M.Rebellato, J.Cai, J.Hopfield, K.P.Briley, C.E.Haisch, P.G.Catrou, P.Bolin, K.Parker, W.T.Kendrick, S.A.Kendrick, R.C.Harland and P.I.Terasaki
Reports have associated non-HLA antibodies, specifically those against angiotensin IItype-1receptor(AT1R), with antibody-mediated kidney graft rejection. However, association of anti-AT1R with graft failure had not been demonstrated. We tested anti-AT1R and donorspecific 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 rafts (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 p¼0.007). Multivariate analysis showed that de novo anti-AT1R was anindependent predictorof graft failure in theABG, 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.
Keywords: Angiotensin II type-1 receptor antibodies, AT1R, DSA, kidney transplantation, rejection