WIP 158 - Impact of Non-HLA antibodies on FSGS reoccurrence and prognosis post transplant

Poster Number: WIP 158
Publication Number: WIP 158.999

Background: Antibodies against human leukocyte antigens (HLAs) are well known to mediate kidney allograft injury. Increasingly, there is recognition that antibodies to non-HLA targets also contribute to antibody-mediated injury. Autoantibodies to Angiotensin II type 1 receptor (AT1R-Ab) and Endothelin type A receptor (ETAR-Ab) are among the most well described non-HLA antibodies associated with rejection, allograft loss, and decline in kidney function. AT1R and ETAR-Abs can directly activate their respective receptors and provoke inflammatory responses in endothelial and vascular smooth muscle cells. Preliminary data also suggest AT1R-Abs may be associated with development of post-transplant recurrence of focal segmental glomerulosclerosis (FSGS). We hypothesize that AT1R and ETAR-Abs are associated with the development of FSGS recurrence. AT1R and ETAR-Abs may cause activation of the AT1R and ETAR receptors on podocytes leading to podocyte injury, glomerular endotheliosis and proteinuria.

Objective: In this study, we aim to assess the association between AT1R-Abs and ETAR-Abs and the development of post-transplant FSGS, decline in renal function, and development of rejection in pediatric kidney transplant recipients with FSGS.

Design/Methods: A cohort of 30 pediatric kidney transplant recipients with end stage renal disease secondary to FSGS have been identified. All patients have been tested for AT1R-Abs and ETAR-Abs both pre- and post-transplant and have clinical data collected to 5-years post-transplant as part of other studies. We will use logistic regression models to evaluate the relationship between AT1R-Ab and ETAR-Ab positivity (> 17 units/mL and > 10 units/mL respectively) and the development of post-transplant FSGS at both 1 and 5 years post-transplant. As secondary outcomes, we will also assess the relationship between AT1R-Ab and ETAR-Ab positivity and rejection and decline in renal function in pediatric patients with FSGS. Our IRB has been accepted pending modifications. We expect to complete analysis in the next 3 months.