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Update on C1 Esterase Inhibitor in Human Solid Organ Transplantation

Berger, Mel MD, PhD1; Lefaucheur, Carmen MD2,3; Jordan, Stanley C. MD4

doi: 10.1097/TP.0000000000002717

Complement plays important roles in both ischemia-reperfusion injury (IRI) and antibody-mediated rejection (AMR) of solid organ allografts. One approach to possibly improve outcomes after transplantation is the use of C1 inhibitor (C1-INH), which blocks the first step in both the classical and lectin pathways of complement activation and also inhibits the contact, coagulation, and kinin systems. C1-INH can also directly block leukocyte-endothelial cell adhesion. C1-INH contrasts with eculizumab and other distal inhibitors, which do not affect C4b or C3b deposition or noncomplement pathways. Authors of reports on trials in kidney transplant recipients have suggested that C1-INH treatment may reduce IRI and delayed graft function, based on decreased requirements for dialysis in the first month after transplantation. This effect was particularly marked with grafts with Kidney Disease Profile Index ≥ 85. Other clinical studies and models suggest that C1-INH may decrease sensitization and donor-specific antibody production and might improve outcomes in AMR, including in patients who are refractory to other modalities. However, the studies have been small and often only single-center. This article reviews clinical data and ongoing trials with C1-INH in transplant recipients, compares the results with those of other complement inhibitors, and summarizes potentially productive directions for future research.

1 CSL Behring, King of Prussia, PA.

2 Paris Translational Research Center for Organ Transplantation, INSERM, Paris, France.

3 Department of Nephrology and Kidney, Transplantation, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.

4 Comprehensive Transplant Center, Cedars-Sinai Medical Center, West Hollywood, CA.

Received 2 November 2018. Revision received 5 February 2019.

Accepted 18 February 2019.

Technical assistance was provided by Mary Beth Moncrief, PhD, and Michael Shaw, PhD, Synchrony Medical Communications, LLC, West Chester, PA, under the direction of the authors. This work was supported by CSL Behring LLC, King of Prussia, PA.

M.B. is an employee of CSL Behring and owns stock in the company. C.L. reports no conflicts of interest. S.C.J. is a consultant for CSL-Behring, Vitaeris, and Hansa Medical. S.C.J. also has received research grants from CSL-Behring, Vitaeris, and Hansa Medical. The other authors declare no conflicts of interest.

All of the authors participated in data/information analysis, researching, planning, writing, and critically reviewing/editing the article. All authors approved the final version of the article.

Correspondence: Melvin Berger, MD, PhD, Global Medical Affairs, CSL Behring LLC, 1040 First Ave, King of Prussia, PA 19406. (

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.