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Angiotensin II Type 1 Receptor Antibodies are Associated with Younger Age and Renal Dysfunction in Pediatric Kidney Transplantation

M. Pearl1, E. T. Chambers2, A. Kirk2, R. Garro3, B. L. Warshaw3, P. Grimm4, R. Ettenger1, E. Reed1

1UCLA, Los Angeles, CA, 2Duke, Durham, NC, 3Emory, Atlanta, GA, 4Stanford, Stanford, CA

Meeting: 2020 American Transplant Congress

Abstract number: 138

Keywords: Antibodies, Autoimmunity, Kidney, Pediatric

Session Information

Session Name: Kidney: Pediatrics

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

 Presentation Time: 3:15pm-3:27pm

Location: Virtual

*Purpose: The significance of non-HLA antibodies in renal transplantation remains unclear. In small single center retrospective studies, angiotensin II type 1 receptor antibody (AT1R-Ab) has been found to be highly prevalent in pediatric kidney transplant recipients (KTRs), in contrast to adults, and associated with vascular inflammation and decline in renal function. We aimed to investigate the prevalence, risk factors for development, and clinical impact of AT1R-Ab in a prospective, multi-center cohort of pediatric KTRs.

*Methods: The Immune Development in Pediatric Transplantation (IMPACT) (Clinicaltrials.gov NCT00951353) study was a prospective, multi-center, observational study of pediatric KTRs in the first year post-transplant evaluating factors affecting alloimmunity. Demographic and clinical data were collected and renal function was serially assessed using the updated Schwartz formula. Blood samples were collected pre-transplant and at months 1, 3, 6, 9, and 12 post-transplant and evaluated for HLA DSA, MICA-Ab, and viremia. Protocol biopsy samples from months 6 and 12 and for clinical indication were evaluated for rejection. Blood samples from 98 patients at pre-transplant and at times of biopsy were tested for AT1R-Ab (ELISA) with >17 U/mL being considered positive.

*Results: The prevalence of patients positive for AT1R-Ab at any time point was 38% (37/98). Of those 37 patients, 28 had AT1R-Ab pre-transplant while 9 developed AT1R-Ab post-transplant. Analysis revealed that younger patients were at higher risk of AT1R-Ab positivity (p<0.0001, Table 1). AT1R-Ab was not associated with viral or bacterial infection, viremia, HLA DSA, or rejection (Table 1). There were 2 allograft losses, both in the AT1R-Ab positive group. AT1R-Ab was associated with greater declines in eGFR over the follow up period (p=0.03, Figure 1).

*Conclusions: AT1R-Ab was highly prevalent, especially in younger children, and associated with greater declines in renal function within the first year post-transplantation. This study confirms the potential detrimental impact of AT1R-Ab on clinical outcomes and the need for further studies to understand the pathophysiology of this relationship and potential benefit of intervention with AT1R blockade.

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To cite this abstract in AMA style:

Pearl M, Chambers ET, Kirk A, Garro R, Warshaw BL, Grimm P, Ettenger R, Reed E. Angiotensin II Type 1 Receptor Antibodies are Associated with Younger Age and Renal Dysfunction in Pediatric Kidney Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/angiotensin-ii-type-1-receptor-antibodies-are-associated-with-younger-age-and-renal-dysfunction-in-pediatric-kidney-transplantation/. Accessed May 16, 2025.

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