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C1‐Inhibitor for treatment of acute vascular xenograft rejection in cynomolgus recipients of h‐DAF transgenic porcine kidneys
Author(s) -
Vangerow Burkhard,
Hecker Jens M.,
Lorenz Ralf,
Loss Martin,
Przemeck Michael,
Appiah Richard,
Schmidtko Jan,
Jalali Arman,
Rueckoldt Horst,
Winkler Michael
Publication year - 2001
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1034/j.1399-3089.2001.00130.x
Subject(s) - xenotransplantation , immunosuppression , complement system , medicine , transplantation , transgene , kidney transplantation , cyclophosphamide , immunology , kidney , regimen , pharmacology , andrology , biology , antibody , chemotherapy , biochemistry , gene
Abstract: At present, the major barrier to successful discordant xenotransplantation of unmodified or complement regulator transgenic porcine xenografts is acute vascular xenograft rejection (AVR). AVR is associated with the intragraft deposition of induced recipient xenoreactive antibodies and subsequent complement activation. In a life‐supporting pig to primate kidney xenotransplantation setting using h‐DAF transgenic donor organs and postoperative immunosuppression, episodes of AVR were either treated with boluses of cyclophosphamide and steroids or with the same regimen supplemented by a three‐day course of C1‐Inhibitor, a multifunctional complement regulator. In 8 out of 10 animals stable initial graft function was achieved; in all animals one or more episodes of AVR were observed. When, in 4 animals, C1‐Inhibitor was added to the standard anti‐rejection treatment regimen, AVR was successfully reversed in 6 out of 7 episodes, while in another group of 4 animals receiving the standard anti‐rejection treatment 0 out of 4 episodes of AVR responded to treatment. Response to anti‐rejection treatment was associated with a significant increase in recipient survival time. We conclude that AVR of h‐DAF transgenic porcine kidneys can be successfully treated by additional short‐term fluid phase complement inhibition.