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Ischemia Reperfusion Injury & Risk for Antibody Mediated Rejection (ABMR) in HLA Sensitized Patients Treated with C1 Esterase Inhibitor (C1INH)

A. Vo,1 O. Aubert,2 J. Choi,1 N. Ammerman,1 H. Edmund,1 A. Peng,1 R. Najjar,1 S. Supreet,1 S. Jordan.1

1Kidney Transplant, Cedars-Sinai Medical Center, LA, CA
2Paris Translational Research for Organ Transplantation, Necker Hospital, Paris, France.

Meeting: 2018 American Transplant Congress

Abstract number: 19

Keywords: Glomerular filtration rate (GFR), Highly-sensitized, Ischemia, Kidney transplantation

Session Information

Session Name: Concurrent Session: Kidney Acute Antibody Mediated Rejection

Session Type: Concurrent Session

Date: Sunday, June 3, 2018

Session Time: 2:30pm-4:00pm

 Presentation Time: 2:30pm-2:42pm

Location: Room Hall 4B

Introduction: Ischemia reperfusion injury (IRI) contributes to delayed graft function (DGF). IRI/DGF in HLA-sensitized (HS) patients likely activates innate and memory injury pathways that may contribute to poor outcomes. C1INH is a serpin (serine protease inhibitor) that inhibits the classic and mannose binding lectin/mannose associated serine protease pathways (MBL/MASP). Here we report outcomes of a Phase I/II placebo-controlled study investigating the safety & efficacy of C1INH to reduce DGF in a cohort of HS patients receiving DD kidney transplants after desensitization. (NCT#02134314). Patients & Methods: From November 2014- February 2017, 70 HS & Non-HS patients were enrolled & randomized 1:1 to receive C1INH 50U/kg (n=35) vs. Placebo (n=35) intra-operatively & 24hrs later. Of the 70 patients, 17 were HLA sensitized and their outcomes are analyzed here. Results: Seventeen HS patients with risks for DGF were randomized: {G1:C1INH (n=10) vs. G2:Placebo (n=7)}. Briefly, CPRA 99-100% & previous transplants were equivalent in G1 & G2. Pre-implantation biopsies were similar. Though not significant, need for dialysis @3-4 weeks post-transplant was 0% (G1) vs. 26% (G2) {Fig 1}. ABMR+TG occurred in 2 patients (20%) in G1 @16M & @30M. In G2, ABMR+TMA occurred in 1 patient @<1M and in another patient, dnDSA induced ABMR occurred @6M post-transplant. No graft loss (0%) occurred in G1, but 2 (29%) occurred in G2 {BKAN (1), ABMR (1)}. No significant differences in eGFR @12M & 24M were seen, G1: 65±21 & 65±12 vs. G2: 55±3 & 50±16 (P=NS) {Fig 2}. Conclusions: C1INH appeared to offer a benefit in HS patients (CPRA 99-100%) in protecting patients from early ABMR associated graft loss. Though not significant, need for dialysis @3-4 weeks as well as renal function @12M & 24M post transplant were numerically superior in C1INH treated group. Therefore, prevention strategies with emphasis on therapeutic targets could improve long-term outcomes in patients w. IRI/DGF.

CITATION INFORMATION: Vo A., Aubert O., Choi J., Ammerman N., Edmund H., Peng A., Najjar R., Supreet S., Jordan S. Ischemia Reperfusion Injury & Risk for Antibody Mediated Rejection (ABMR) in HLA Sensitized Patients Treated with C1 Esterase Inhibitor (C1INH) Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Vo A, Aubert O, Choi J, Ammerman N, Edmund H, Peng A, Najjar R, Supreet S, Jordan S. Ischemia Reperfusion Injury & Risk for Antibody Mediated Rejection (ABMR) in HLA Sensitized Patients Treated with C1 Esterase Inhibitor (C1INH) [abstract]. https://atcmeetingabstracts.com/abstract/ischemia-reperfusion-injury-risk-for-antibody-mediated-rejection-abmr-in-hla-sensitized-patients-treated-with-c1-esterase-inhibitor-c1inh/. Accessed June 6, 2025.

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