Non-HLA Antibodies to G Protein-Coupled Receptors and Allograft Survival in Pediatric Kidney Transplant Recipients: Short- and Long-Term Outcomes
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 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.
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 5, 2025.« Back to 2022 American Transplant Congress