Pre-transplant angiotensin II type 1 receptor antibodies and anti-endothelial cell antibodies predict graft function and allograft rejection in a low-risk kidney transplantation setting

Background: Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (antiAT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients. Methods: In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes. Results: Pre-transplant anti-AT1Rs (≥ 11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P = 0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P = 0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥ 11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P < 0.001; P = 0.028), although the risk of AR was not significant. Conclusions: Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.