Effect of anti-angiotensin II type 1 receptor antibodies on the outcomes of kidney transplantation: a systematic review and meta-analysis

BACKGROUND: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been recognized as non-human leukocyte antigen antibodies associated with allograft rejection and poor allograft outcomes after kidney transplantation. The aim of this study was to assess the risk anti-AT1R-Abs pose for rejection and graft loss among kidney transplant (KT) populations. METHODS: We systematically searched PubMed, Embase and the Cochrane Library databases for relevant articles published from inception until June 2021 to identify all studies concerning the role AT1R-Abs play in the clinical outcome after kidney transplantation. Two reviewers independently identified studies, abstracted outcome data and assessed the quality of the studies. The meta-analysis was summarized using fixed-effects or random-effects models, according to heterogeneity. The major outcomes included delayed graft function, acute rejection, graft loss or patient death after transplantation. RESULTS: Twenty-one eligible studies involving a total of 4023 KT recipients were included in the evaluation. Meta-analysis results showed that the AT1R-Ab-positive KT group had a greater incidence of antibody-mediated rejection {relative risk [RR] 1.94 [95% confidence interval (CI) 1.61-2.33]; P < 0.00001} and graft loss [RR 2.37 (95% CI 1.50-3.75); P = 0.0002] than did the AT1R-Abs-negative KT group. There was no significant statistical difference in delayed graft function rate, T-cell-mediated rejection, mixed rejection, acute cellular rejection, acute rejection and patient death rate between the AT1R-Ab-positive KT and AT1R-Ab-negative KT groups. CONCLUSIONS: Our study shows that the presence of anti-AT1R-Abs was associated with a significantly higher risk of antibody-mediated rejection and graft loss in kidney transplantation. Future studies are still needed to evaluate the importance of routine anti-AT1R monitoring and therapeutic targeting. These results show that assessment of anti-AT1R-Abs would be helpful in determining immunologic risk and susceptibility to immunologic events for recipients.