Date: Monday, June 3, 2019
Session Time: 2:30pm-4:00pm
Presentation Time: 3:18pm-3:30pm
Location: Veterans Auditorium
*Purpose: Current state-of-the-art pre-transplant risk stratification relies on the HLA system. Non-HLA agonistic angiotensin II type 1 receptor antibodies (AT1R-Ab) have been associated with allograft rejection. We investigated whether AT1R-Ab might improve current approach to pre-transplant immunological risk assessment.
*Methods: We enrolled a prospective cohort of 1845 kidney recipients transplanted across a negative complement-dependent cytotoxicity crossmatch between 2008-2013. Patients were assessed at the time of transplantation for donor, recipient and transplant characteristics, circulating anti-HLA donor-specific antibodies (HLA-DSAs) and AT1R-Ab using quantitative ELISA. Primary outcome was allograft loss until 2018.
*Results: We identified 438 (24%) patients with pre-transplant AT1R-Ab (>10 U/mL). Patients with AT1R-Ab showed decreased 8-year graft survival (73%, 95%CI: 68-77) compared to patients without AT1R-Ab (86%, 95%CI: 83-87, p<0.001). Pre-transplant AT1R-Ab and HLA-DSAs had a synergistic deleterious effect: 8-year graft survival of 65% (95%CI: 55-73) in patients with both antibodies (n=132), 76% (95%CI: 69-81) in those with HLA-DSAs alone (n=210), 76% (95%CI: 71-81) in those with AT1R-Ab alone (n=306) and 87% (95%CI: 85-89) in those without antibodies (n=1197) (p<0.001). Spline modeling showed dose-response effect between AT1R-Ab level and the risk of graft loss (p<0.001). Pre-transplant AT1R-Ab were associated with antibody-mediated rejection (OR=2.20, 95%CI=1.69-2.87, p<0.001) and graft loss (adjusted HR=2.04, 95%CI=1.59-2.62, p<0.001) after adjusting on donor (age, gender, type, cause of death), recipient (age, gender, calculated panel reactive antibody, previous transplant, time since dialysis) and transplant (HLA-A, -B, -DR, and -DQ mismatches, pre-transplant anti-HLA DSAs, cold ischemia time, induction therapy) characteristics. Pre-transplant AT1R-Ab assessment improved risk prediction for graft loss compared to conventional pre-transplant parameters (NRI=0.31, p<0.001).
*Conclusions: Pre-transplant risk assessment can be improved by measuring AT1R-Ab antibodies in kidney recipients, independently from the presence of pre-transplant HLA-DSAs.
To cite this abstract in AMA style:Lefaucheur C, Viglietti D, Bouatou Y, Philippe A, Pievani D, Aubert O, Glotz D, Legendre C, Loupy A, Dragun D. Angiotensin II Type 1 Receptor Antibodies Improve Risk Stratification for Kidney Allograft Outcomes at the Time of Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/angiotensin-ii-type-1-receptor-antibodies-improve-risk-stratification-for-kidney-allograft-outcomes-at-the-time-of-transplantation/. Accessed December 5, 2020.
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