Angiotensin II type 1 receptor antibodies in kidney transplantation: An evidence-based comprehensive review.

Angiotensin II type 1 receptor antibodies (AT1R-Ab) are among the most investigated types of non-HLA antibodies in kidney transplantation. Our aim is to provide an update regarding the clinical relevance of AT1R-Ab by outlining their prevalence, testing methodology, mechanism of graft injury and the association with graft rejection phenotypes, the relationship with HLA-donor specific antibodies (DSA) and some therapeutic aspects. To accomplish these, we performed a literature review between 2005 and 2019, identifying 27 relevant studies for inclusion. The reported prevalence of these antibodies is widely variable in part related to testing variability and lack of a standardized threshold for positivity. Data available suggest that both pre-formed and de novo antibodies are associated with negative graft outcomes. The pathogenesis of AT1R-Ab mediated graft injury seems to be complement-independent. Different phenotypes of antibody-mediated, T-cell-mediated and vascular rejection have been described in patients with AT1R-Ab. The relationship between HLA-DSA and AT1R-Ab is mutual in terms of their development, including a complex process between alloimmunity, autoimmunity, inflammation, endothelial damage and antigen expression. Antibody double positivity had a synergistic negative effect associated with detrimental effects on graft outcomes. Understanding the complexity of AT1R-Ab mediated graft injury and the relationship with HLA-DSA in kidney transplantation could provide a complementary, integrated assessment of immunological risk, help stratify the risk of graft rejection and dysfunction and may guide the treatment approach.