The effect of various techniques to eliminate natural preformed antibo
dies (IgM/IgG) in a discordant kidney xenograft model are reported. Th
e combination of multiple plasmapheresis, splenectomy and immunosupres
sive drugs allowed to prolong kidney xenograft survival until three we
eks when without treatment such a graft would be rejected within hours
or minutes. To prevent the rebound of preformed antibodies, the assoc
iation of multiple plasmapheresis and anti-IgM monoclonal antibodies s
eem to be efficient in such a model. The combination of a pig liver pe
rfusion, a sublethal total body irradiation, a bone marrow graft and v
arious drugs prolonged kidney xenograft survival up to 2 weeks with so
me signs of peripheral microchimerism. Advantages and disadvantages of
each techniques are discussed.