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

Abstract

Background Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been recognized as non-HLA 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 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 the fixed-effects models 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 4,023 kidney transplantation recipients were included in the evaluation to identified. Meta-analysis results showed that the AT1R-Ab positive kidney transplant (KT) group had a greater incidence of antibody-mediated rejection (RR = 1.94, 95%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 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 shows that assessment of anti-AT1R-Abs would be helpful in determining immunologic risk and susceptibility to immunologic events for recipients.

Non-HLA Antibodies to G Protein–coupled Receptors in Pediatric Kidney Transplant Recipients: Short- and Long-term Clinical Outcomes

“…Clinical studies examining the association between AT1R-Ab and clinical outcomes have been highlighted in a recent review 32 and meta-analysis. 8 Most studies have focused on pretransplant AT1R-Ab and short-term allograft outcomes. Interestingly, one adult study found that patients with high pretransplant AT1R-Ab had a higher risk of rejection in the first 4 mo posttransplant, but a higher risk of allograft loss only after 3 y posttransplant.…”

“…AT1R-Ab and ETAR-Ab have been associated with AMR, vascular pathology, increased cytokines, and allograft dysfunction in KTRs. [3][4][5][6][7][8][9][10] The mechanisms of injury remain unclear; both classical mechanisms of antibody-mediated allograft injury and overactivation of G protein-coupled receptors may contribute to the clinical findings. 3,11,12 We and others [13][14][15][16] have recently reported the increased prevalence of AT1R-Ab and ETAR-Ab in pediatric KTRs.…”

Clinical conundrums in pediatric kidney transplantation: What we know about the role of angiotensin II type I receptor antibodies in pediatric kidney transplantation and the path forward

“…In the literature, positive cutoffs associated with adverse outcomes range from 9 to 17 U/mL. 14 Based on our receiver operating characteristic curve analysis and the known association between younger age and high AT1R-Ab levels, we generally use >17 U/mL as a positive cutoff for our pediatric kidney transplant recipients. 17 However, in different contexts, levels as low as 9.5 U/mL may be relevant.…”

“…17,22 A recent meta-analysis provides a full table of studies in adults and pediatric patients on this topic with annotation of studies looking at pre-and post-transplant AT1R-Abs. 14 Despite the availability of these studies, the question of how to treat patients with a positive pre-transplant test is a controversial one.…”

The Pre-Transplant Non-HLA Antibody Burden Associates With the Development of Histology of Antibody-Mediated Rejection After Kidney Transplantation

“…While the number of publications linking non-HLA antibodies to the development of ABMR histology (ABMR h ) is growing, it is still unclear how these non-HLA antibodies contribute to kidney allograft damage and graft failure. Currently, there is inadequate consensus for routine testing of any non-HLA antibody for diagnosing ABMR (8)(9)(10)(11)(12), although there is growing literature on the role of anti-angiotensin receptor II type 1 antibodies as risk factor for ABMR and graft failure and for potential future clinical implementation (13,14).…”