Ex Vivo Spleen and Kidney Absorption of Xenoreactive Natural Antibodies Decreases Severity of Hyperacute Rejection in Pig-to-dog Renal Xenotransplantation

The severe hyperacute rejection in pig-to-dog renal xenotransplantation is mainly caused by xenoreactive natural antibodies (NAb). Organ absorption (ex vivo perfusion of spleen and kidney of donor species) was performed to remove xenoreactive NAb. A pig-to-dog renal transplantation model was used for discordant combination xenografting. The experimental animals were divided into 4 groups: group 1, control; group 2, recipients splenectomized prior to renal xenografting; group 3, splenectomy along with ex vivo spleen xenoreactive NAb absorption; and group 4, splenectomy along with ex vivo spleen and kidney xenoreactive NAb absorption. After the pretransplant treatment of the recipients, the serum titer of anti-pig lymphocytotoxic antibodies, hemagglutination antibodies, IgG and IgM were determined. Postoperative assessment was made of urine output and the rejected kidneys examined histopathologically. The serum titer of all measured antibodies markedly decreased after sequential pig spleen/ kidney absorption. Total urine output was significantly larger in group 4 than in group 1. The histopathological findings revealed that the severity of hyperacute rejection was markedly decreased in groups 3 and 4 compared to groups 1 and 2. These results indicate that ex vivo absorption using donor spleen and kidney is useful in preoperative removal of xenoreactive NAb and prolongs renal xenograft survival.