Use of von Willebrand diseased kidney as donor in a pig-to-primate model of xenotransplantation

Background The coagulation process in hyperacute and delayed xenograft reje ction is essential and depends upon platelet adhesion and aggregation. The initial binding of platelets to the damaged endothelium is due to the inter action of the platelet receptor glycoprotein Ib with von Willebrand factor (vWF), which is present on activated endothelial cells and bound to the sub endothelial matrix. We hypothesized that the use of organs from animals wit h homozygous von Willebrand disease (vWD), severely deficient in vWF, might prevent the thrombosis encountered in delayed xenograft rejection. Methods. Ten baboons were treated by extracorporeal immunoadsorption of xen oreactive natural antibodies (XNA) through the donor pig liver to inhibit h yperacute rejection and received heterotopic vWD or control pig kidney xeno grafts. XNA levels, coagulation, and platelet activation markers were studi ed, and specimens of rejected kidneys were analyzed histologically. Results. Although XNA depletion was comparable in both groups, neither kidn ey function nor survival times of control (n=5) or vWD (n=5) porcine kidney s showed any difference. Platelet and coagulation activation was evidenced in both groups after surgery and at rejection time. Immunohistochemical ana lysis revealed a weak endothelial vWF immunostaining in the rejected vWD ki dneys, whereas it was undetectable in the nongrafted vWD kidneys, suggestin g the deposition of baboon plasma vWF on the porcine vessels. Conclusions. The use of vWD organs did not improve the survival time of gra fted kidneys in this xenotransplantation model. Further studies on the use of vWD organs, in association with other therapeutic approaches, such as co mplement inhibition, are nevertheless necessary to evaluate the usefulness of vWF deficiency as an adjunctive therapy to decrease the coagulation proc ess during xenograft rejection.