학술논문
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.
Document Type
Article
Author
Source
Subject
*RECEPTOR antibodies
*IMMUNOGLOBULINS
*
Language
ISSN
1320-5358
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. Summary at a Glance: Antibody‐mediated rejection in renal transplantation is a major cause of short‐ and long‐term graft loss. The possible synergistic effects of the anti‐angiotensin II type I receptor antibody and anti‐HLA antibodies is addressed by the present study and similar larger studies may allow further stratification of patients at risk of graft loss and personalised management protocols. [ABSTRACT FROM AUTHOR]