Date: Monday, June 13, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Delayed graft function (DGF) is associated with decreased kidney graft survival. We have shown that pre-transplant anti-LG3 autoantibodies were associated with increased risk of DGF and early graft dysfunction in kidney transplant recipients (KTR) and decreased renal function in a murine model of ischemia reperfusion injury (IRI). Now we ask whether pre-transplant titers of anti-LG3 and other transplant-relevant autoantibodies are associated with 1-year graft function in KTR with DGF, and whether anti-LG3 IgGs can enhance renal microvascular rarefaction and fibrosis.We performed a single center, retrospective cohort study in consecutive KTR transplanted between June 1st 2008 and 2013 without rejection. DGF was defined as the need for dialysis in the first week or failure of sCr to decrease by ˃10% on the first 3 days post-transplant. Anti-LG3, anti-vimentin and anti-angiotensin II type 1 receptors (anti-ATII1R) were measured immediately prior to transplantation using ELISA. 1 year eGFR was estimated with the 4-variable MDRD equation. Unilateral renal artery clamping for 30 minutes plus contra-lateral nephrectomy were performed in C57Bl/6 mice. Intra-venous injections of anti-LG3 IgGs or control IgGs were performed every other day starting 2 days pre-surgery.Among 130 participants, 39 experienced DGF. There was no association between the titers of three autoantibodies. Elevated pre-transplant anti-LG3 titers (β: -13 ml/min/1.73m2, 95% CI: -25, -1 for 3rd versus 1st tertile) were associated with reduced 1 year eGFR in patients with DGF (adjusted for donor age) but not in those with immediate graft function, while anti-vimentin and anti-ATII1R were not. Mice passively transferred with anti-LG3 IgGs had higher BUN levels at day 2 post-IRI (p=0.04), decreased CD31 staining (p<0.001) and increased alpha-SMA staining (p<0.001) on immunohistochemistry at day 7 post-IRI. Together these results demonstrate that anti-LG3 antibodies but not anti-ATII1R or anti-vimentin are associated with decreased 1-year graft function in patients with DGF. This may be explained by anti-LG3 induced renal microvascular rarefaction and fibrosis in the context of IRI.
CITATION INFORMATION: Yang B, Hamelin K, HÉnault-Rondeau M, Patey N, Turgeon J, Lan S, Pomerleau L, Peng J, Tremblay J, DieudÉ M, HÉbert M.-J, Cardinal H. Anti-LG3 Antibodies Enhance Renal Microvascular Rarefaction, Fibrosis and Dysfunction Associated with Ischemia-Reperfusion Injury. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Yang B, Hamelin K, HÉnault-Rondeau M, Patey N, Turgeon J, Lan S, Pomerleau L, Peng J, Tremblay J, DieudÉ M, HÉbert M-J, Cardinal H. Anti-LG3 Antibodies Enhance Renal Microvascular Rarefaction, Fibrosis and Dysfunction Associated with Ischemia-Reperfusion Injury. [abstract]. Am J Transplant. 2016; 16 (suppl 3). http://atcmeetingabstracts.com/abstract/anti-lg3-antibodies-enhance-renal-microvascular-rarefaction-fibrosis-and-dysfunction-associated-with-ischemia-reperfusion-injury/. Accessed December 18, 2017.
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