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Evaluation of Post-Transplant Angiotensin II Type 1 Receptor Antibodies, Donor-Derived Cell-Free DNA, and Rejection in Heart Transplant Recipients

B. Agegnehu1, S. Sterling1, R. Winstead1, I. Tchoukina2

1Pharmacy, VCU Health System, Richmond, VA, 2Advanced Heart Failure and Transplant Cardiology, VCU Health System, Richmond, VA

Meeting: 2022 American Transplant Congress

Abstract number: 240

Keywords: Antibodies, Heart transplant patients, Rejection

Topic: Clinical Science » Heart » 63 - Heart and VADs: All Topics

Session Information

Session Name: Heart and VADs: All Topics II

Session Type: Rapid Fire Oral Abstract

Date: Monday, June 6, 2022

Session Time: 3:30pm-5:00pm

 Presentation Time: 4:30pm-4:40pm

Location: Hynes Room 210

*Purpose: There is limited evidence evaluating the relationship between angiotensin II type 1 receptor antibodies (AT1R-Abs), donor-derived cell-free DNA (dd-cfDNA), and rejection in heart transplant recipients (HTRs). Data is also limited on the management of AT1R-Abs with angiotensin receptor blockers (ARBs) in HTRs.

*Methods: This was an institutional review board approved retrospective review of adult HTRs at VCU Health between 01/2016 and 12/2020 who had dd-cfDNA performed within 30 days of a biopsy and AT1R-Ab levels drawn post-transplant. Multiorgan and retransplant recipients were excluded. The primary outcome evaluated the relationship of post-transplant AT1R-Abs and dd-cfDNA on antibody-mediated rejection (AMR) and acute cellular rejection (ACR). The secondary outcome evaluated the effect of ARB initiation in HTRs with positive AT1R-Abs on AMR and ACR. Categorical variables were analyzed through chi-squared and continuous variables through student’s t-test. Pearson’s coefficient was used for correlation analysis.

*Results: A total of 43 HTRs were included. Median time from transplant to first AT1R-Ab and dd-cfDNA were 11 (4, 24) months and 9 (7, 23) months, respectively. Most patients were not sensitized with a mean class I and class II PRA of 4.6% and 6.6%, respectively. There was a clinically relevant trend towards higher mean peak AT1R-Ab levels in the 5 HTRs who had AMR within 1-year post-transplant versus the 38 HTRs without (34.9 vs 24.1 U/mL, p=0.53). This trend of higher mean peak AT1R-Ab levels persisted in 8 HTRs with overall AMR past 1-year post-transplant versus the 35 HTRs without (31.2 vs 24.0 U/mL, p=0.55). Similarly, there was a trend towards higher mean peak AT1R-Ab levels in 8 HTRs with ACR within 1-year post-transplant versus the 35 HTRs without (46.1 vs 20.6 U/mL, p=0.27) as well as in the 10 HTRs with overall ACR past 1-year post-transplant versus the 33 HTRs without (40.1 vs 20.1 U/mL, p=0.29). Elevated mean peak dd-cfDNA in the 8 HTRs with overall AMR versus the 29 HTRs without was seen (1.1 vs 0.31, p=0.20). A correlation between AT1R-Ab levels and dd-cfDNA was not observed (r2=0.004). The addition of an ARB resulted in a mean decrease in AMR grading of 0.25 (p=0.12) and a mean ACR grading difference of 0.05 (p=0.63).

*Conclusions: There was a clinical trend towards higher AT1R-Ab levels in HTRs with AMR or ACR post-transplant, compared with those who did not have rejection. There were additional trends towards ARB initiation decreasing the grade of AMR as well as dd-cfDNA rising in AMR. One limitation of this study was that the median time from transplant to first AT1R-Ab level was close to a year post-transplant, and most rejection episodes occurred within 1-year post-transplant. Future larger studies are warranted to validate the results of this study.

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To cite this abstract in AMA style:

Agegnehu B, Sterling S, Winstead R, Tchoukina I. Evaluation of Post-Transplant Angiotensin II Type 1 Receptor Antibodies, Donor-Derived Cell-Free DNA, and Rejection in Heart Transplant Recipients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/evaluation-of-post-transplant-angiotensin-ii-type-1-receptor-antibodies-donor-derived-cell-free-dna-and-rejection-in-heart-transplant-recipients/. Accessed May 11, 2025.

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