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Peer-reviewedCC BY 4.0Frontiers in Immunology

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

  • Jayeon Ahn1
  • Sangwan Kim1,2
  • Ahram Han1
  • Jongwon Ha1,3
  • Ara Cho1
  • Donghoon Jeong1
  • Hajeong Lee4
  • Yong Chul Kim4
  • Sangil Min1,3
4 affiliations
  1. 1Department of Surgery, Seoul National University College of Medicine
  2. 2Biomedical Research Institute, Seoul National University Hospital
  3. 3The Transplantation Research Institute, Medical Research Center, Seoul National University College of Medicine
  4. 4Department of Internal Medicine, Seoul National University Hospital
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{ahn2026longitudinal,
  title = {{Longitudinal dynamics of angiotensin II type 1 receptor antibodies around kidney transplantation and their impact on clinical outcomes}},
  author = {Jayeon Ahn and Sangwan Kim and Ahram Han and Jongwon Ha and Ara Cho and Donghoon Jeong and Hajeong Lee and Yong Chul Kim and Sangil Min},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1960231},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960231/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Longitudinal dynamics of angiotensin II type 1 receptor antibodies around kidney transplantation and their impact on clinical outcomes
AU  - Jayeon Ahn
AU  - Sangwan Kim
AU  - Ahram Han
AU  - Jongwon Ha
AU  - Ara Cho
AU  - Donghoon Jeong
AU  - Hajeong Lee
AU  - Yong Chul Kim
AU  - Sangil Min
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1960231
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960231/full
AB  - 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.
SN  - 1664-3224
ER  -