Longitudinal dynamics of angiotensin II type 1 receptor antibodies around kidney transplantation and their impact on clinical outcomes

Background Angiotensin II type 1 receptor antibody (AT1R-Ab) has been implicated in graft injury after kidney transplantation, but most prior studies relied on single-timepoint measurements and did not capture the antibody’s true longitudinal dynamics. This study evaluated the longitudinal trajectory of AT1R-Ab before and after kidney transplantation and its association with clinical outcomes. Methods We conducted a single-center retrospective cohort study of 241 kidney transplant recipients with serial AT1R-Ab measurements pre-transplant, at 2 weeks, 3 months, and 1 year, along with protocol biopsies at 2 weeks and 1 year. Patients were categorized into LOW (<10 U/mL), GREY (10–17 U/mL), and HIGH (>17 U/mL) groups. Secondary outcomes included renal function, de novo donor-specific antibody (DSA) development, and Banff histopathology. Cox marginal structural models with inverse probability weighting were applied. Results Among the 73 patients classified as GREY or HIGH at baseline, only 14.3% and 17.6%, respectively, remained in their baseline category throughout follow-up, with movement toward the LOW category more common than escalation to a higher category. Consistent with this, the GREY and HIGH groups did not show a significant excess risk of biopsy-proven acute rejection (BPAR) relative to the LOW group at either 1-year (aHR 0.67–1.44) or 3-year (aHR 0.69–1.17) follow-up, nor for de novo DSA at 1-year (aHR 1.59–2.49) or 3-year (aHR 0.89–1.14) follow-up. The initial crude signal for microvascular inflammation (MVI) at 3 years (cHR 4.92, 95% CI 1.57–15.39, p=0.006) did not persist after adjustment (aHR 2.93, 95% CI 0.97–8.85, p=0.057), a pattern also seen at 1 year (crude HR 3.08 vs. adjusted HR 2.86, p=0.063). Conclusion Elevated AT1R-Ab levels around kidney transplantation frequently declined spontaneously, accompanied by favorable clinical outcomes—paralleling findings reported for HLA-DSA and suggesting that antibody-mediated risk may depend less on presence than on change over time. These results provide limited support for universal single-measurement screening and instead support the targeted testing strategy recommended by the 2022 STAR Working Group. Larger prospective studies are needed to confirm these findings.