Session Time: 2:15pm-3:45pm
Presentation Time: 2:39pm-2:51pm
Location: Terrace I-III
Introduction: Desensitization (DES) strategies focus primarily on antibody reduction using IVIG, rituximab ± PLEX to prevent DSA-induced antibody-mediated rejection (ABMR) and rebound B-cell activity. Recently, complement inhibitors, such as anti-C-5 and C1 esterase inhibitor (C1-INH) (Vo et al Transplantation in press) have shown promise in preventing terminal and early complement activation, respectively with prevention of early ABMR episodes. C1-INH blocks the classical and MBSP pathways of complement activation. Here we report long-term outcomes of a placebo-controlled, single center study using C1-INH in HS patients for prevention of ABMR. Patients & Methods: From 12/2011 to 4/2013, 20 consecutive HS patients (2LD/8DD in each group) DES with IVIG + rituximab ± PLEX were enrolled and randomized 1:1 to receive C1-INH (20U/kg/dose) v. Placebo intra-operatively, then 2x weekly x7 doses. All patients underwent protocol biopsy at 6M. This study extents the follow-up to 24M. Results: In the C1-INH group, no patients had ABMR during C1-INH treatment. However, two patients developed ABMR at 1.5M post-tx (1) and 6M post-tx (1). In the placebo group, three patients developed ABMR at 12 days (1), at 3M (1) and at 6M (1) post-tx. One patient in the C1-INH group developed ABMR 2 weeks after the last C1-INH infusion. Only a weak DSA to CW12 was detected, but the patient had a strong AT1R antibody that was retrospectively identified pre-tx and became strong post-tx. The patient had TG on biopsy and was treated with IVIG + rituximab. In the placebo group, another patient developed C4d+ ABMR 3M post-tx w/o DSA but with AT1R+, also treated with IVIG + rituximab + PLEX. One patient in the C1-INH group developed DSA post-tx while 3 in the placebo group developed DSAs, one with documented ABMR with TG at 21M post-tx. Infectious complication remain low with only one patient in the C1-INH group developing BKAN. Renal function at 24M was good (C1-INH 1.05±0.29 v. placebo 1.13±1.2 mg/dl). One patient in the C1-INH group had recurrent FSGS at 6M post-tx that responded well to PLEX + rituximab. Conclusions: AT1R antibodies were responsible for ABMR episodes in both groups. Additional treatment with IVIG + rituximab and PLEX was required. Overall, patients in both groups continue to do well. Additional studies are required to definitively assess the benefits of C1 inhibition post-transplant in HS patients.
To cite this abstract in AMA style:Vo A, Choi J, Kahwaji J, Puliyanda D, Peng A, Villicana R, Jordan S. Long-Term Analysis of a Placebo-Controlled Trial of C1-INH for Prevention of Antibody-Mediated Rejection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/long-term-analysis-of-a-placebo-controlled-trial-of-c1-inh-for-prevention-of-antibody-mediated-rejection/. Accessed April 4, 2020.
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