Deleterious effect of anti‐angiotensin II type 1 receptor antibodies detected pretransplant on kidney graft outcomes is both proper and synergistic with donor‐specific anti‐HLA antibodies

摘要

Abstract Aim Both donor‐specific antibodies (DSA) and anti‐angiotensin II type 1 receptor antibodies (AT1R‐abs) have been associated with poor graft outcomes after kidney transplantation (KT). We aimed to understand the impact of pretransplant AT1R‐abs with or without concomitant DSA on KT outcomes. Methods Seventy‐six patients transplanted in 2009 were studied. DSA (MFI??1000) and/or AT1R‐abs (10UI) were detected by solid‐phase assays in pre‐KT sera. Multivariable Cox regression models were used to determine independent predictors of outcomes: acute rejection (AR) and graft failure. Results At transplant, 48 patients were AT1R‐abs (?)/DSA (?), 12 AT1R‐abs (+)/DSA (?), 9 AT1R‐abs (?)/DSA (+) and 7 AT1R‐abs (+)/DSA (+). Incidence of acute rejection at 1‐year increased from 6% in AT1R‐abs (?)/DSA (?), to 35% in AT1R‐abs (+)/DSA (?), 47% in AT1R‐abs (?)/DSA (+) and 43% in AT1R‐abs (+)/DSA (+) ( P ?0.001). No difference in DSA strength and C1q‐binding ability was observed between AT1R‐abs (?) /DSA (+) and AT1R‐abs (+)/DSA (+) patients. Graft survival at 6‐years was the lowest in AT1R‐abs (+)/DSA (+) (57%), followed by AT1R‐abs (+)/DSA (?) (67%), and higher in AT1R‐abs (?)/DSA (?) (94%) and AT1R‐abs (?)/DSA (+) (89%) patients ( P =?0.012). AT1R‐abs (+)/DSA (?) (HR?=?6.41, 95% CI: 1.43–28.68; P =?0.015) and AT1R‐abs (+)/DSA (+) (HR?=?7.75, 95% CI: 1.56–38.46; P =?0.012) were independent predictors of graft failure. Conclusion Acute rejection incidence and graft failure were associated with both DSA and AT1R‐abs. These results demonstrate a proper negative effect of AT1R‐abs on graft outcomes, besides a synergistic one with DSA. Pretransplant AT1R‐abs should be acknowledged to better stratify patients’ immunological risk.