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Non-HLA Antibodies to G Protein-Coupled Receptors and Allograft Survival in Pediatric Kidney Transplant Recipients: Short- and Long-Term Outcomes

M. Pearl1, L. Chen1, P. Weng1, E. T. Chambers2, E. F. Reed3

1UCLA, Los Angeles, CA, 2Pediatrics, Duke University, Durham, NC, 3Univ of California LA, Los Angeles, CA

Meeting: 2022 American Transplant Congress

Abstract number: 108

Keywords: Alloantibodies, Kidney, Pediatric, Survival

Topic: Clinical Science » Kidney » 43 - Kidney: Pediatrics

Session Information

Session Name: Kidney: Pediatrics

Session Type: Rapid Fire Oral Abstract

Date: Sunday, June 5, 2022

Session Time: 5:30pm-7:00pm

 Presentation Time: 6:10pm-6:20pm

Location: Hynes Ballroom C

*Purpose: We have recently shown that the non-HLA antibodies to angiotensin II type 1 receptor (AT1R-Ab) and endothelin-1 type A receptor (ETAR-Ab) are prevalent and associated with poor outcomes and elevated inflammatory cytokines in pediatric kidney transplant recipients (KTRs) in the first 2 years post-transplant. We aimed to determine the clinical impact of early development of these antibodies on 5 year kidney transplant outcomes in an extended cohort.

*Methods: 100 pediatric KTRs were monitored from August 2005 to April 2017. ETAR-Ab (ELISA, >10 units/mL positive cutoff), AT1R-Ab (ELISA, >17 units/mL positive cutoff), and HLA DSA (Luminex) were measured pre-transplant, 6 months (m), 12m, and 24m post-transplant and during episodes of suspected rejection through the first 2 years post-transplantation. Allograft function was assessed through 5 years post-transplant.

*Results: The prevalence of patients positive for AT1R-Ab or ETAR-Ab in the first 2 years post-transplant was 59%. Median (IQR) AT1R-Ab and ETAR-Ab levels in the antibody positive group were 20.0 (16.1-28.6) and 13.5 (6.8-19.9) units/mL respectively. In antibody positive patients, 56% had preformed antibodies while 44% developed antibodies de novo. Younger age was a risk factor for both preformed and de novo non-HLA antibodies (p=0.011) and deceased donor transplantation was a risk factor for de novo antibody development (p=0.018). De novo AT1R-Ab or ETAR-Ab positivity was associated with allograft loss at 2 years (p=0.018) (Table 1). However, in patients with surviving grafts at 2 years, there was no association between early antibody positivity and allograft loss between 2 and 5 years (Figure 1).

*Conclusions: Pediatric KTRs are at high risk for development of AT1R-Ab and ETAR-Ab post-transplantation. Risk of poor outcomes may be higher in the first 2 years post-transplantation. Further studies are needed to elucidate risk factors and biomarkers for non-HLA associated transplant injury and possible impact of treatment interventions with angiotensin and endothelin receptor blockers.

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To cite this abstract in AMA style:

Pearl M, Chen L, Weng P, Chambers ET, Reed EF. Non-HLA Antibodies to G Protein-Coupled Receptors and Allograft Survival in Pediatric Kidney Transplant Recipients: Short- and Long-Term Outcomes [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/non-hla-antibodies-to-g-protein-coupled-receptors-and-allograft-survival-in-pediatric-kidney-transplant-recipients-short-and-long-term-outcomes/. Accessed May 30, 2025.

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