Background:

Angiotensin II type 1 receptor (AT1R) is highly expressed on the endothelial cells and podocytes, which play an essential role in the maintenance of vascular hemostasis. The presence of antibodies against AT1R (AT1R-Ab) leads to activation of this receptor resulting in endothelial cell dysfunction and podocyte injury. AT1R-Ab may contribute to a wide range of kidney abnormalities including pre-eclampsia, hypertension and glomerular endotheliosis. Here, we assess a correlation between AT1R-Ab positivity and proteinuria and/or post transplant focal segmental glomerulosclerosis (FSGS).

Methods:

This is a retrospective study that included kidney recipients with positive serum AT1R-Ab (>10units/ml) transplanted and followed at our institution between 2009 and 2016. The primary outcome was development of proteinuria defined by urine protein-to-creatinine ratio (UPCR) of >1 g/g and biopsy proven FSGS. A secondary outcome was evidence of antibody-mediated rejection on biopsy.

Results:

We identified 100 patients with positive serum AT1R-Ab at time of kidney transplant biopsy. Thirty-four of the 100 recipients (34%) had UPCR of >1 g/g. Thirty-one (31%) had biopsy proven FSGS and/or significant podocyte effacement (greater than 20% foot process effacement). Nineteen of the 34 (55%) patients who had significant proteinuria had biopsy proven FSGS and 15 (45%) did not have biopsy proven FSGS. Ten of 31 recipients who had biopsy proven FSGS had primary FSGS as the cause of end stage renal disease. 29% of renal transplant recipients had biopsy proven antibody mediated rejection (AMR).

Conclusion:

Our data show a possible association between positive AT1R-Ab and proteinuria/FSGS. AT1R-ab may mediate pathway that contributes not only to AMR but also to the development of de novo and/or recurrent FSGS. This data may help understand the role of AT1R-Abs in a sub-group of post transplant FSGS patients and help identify targeted therapies for this group.

CITATION INFORMATION: Aala A., Philogene M., Alachkar N. Angiotensin II Type 1 Receptor Antibodies as Markers of Post Transplant Focal Segmental Glomerulosclerosis and Proteinuria Am J Transplant. 2017;17 (suppl 3).

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