Attempted Immunological Alteration of Canine Renal Allograft Donors

SUMMARY A significant reduction in the severity of the rejection response has been achieved in dogs receiving renal allografts from donors pretreated i.v. with procarbazine hydrochloride and, cyclophosphamide at 51/2 hr and methylprednisolone at 21/2 hr before harvesting. Procarbazine hydrochloride, both alone and in combination with methylprednisolone, was found to be the most effective in delaying the onset of uremia and in prolonging the survival time. Methylprednisolone in combination with other druggs seemed to provide a prolonged period of excellent renal function preceding eventual uremia, particularly when used in combination with procarbazine hydrochloride. Prolongation of survival may be explained on the basis of three possible mechanisms: (1) the delay of induction of the immune response by modification of the antigenic properties of drug-sensitive nonparenchymal lymphocytes derived from hemopoietic cells (so called passenger leukocytes) that are presumed to be the initiating factor in rejection; (2) delayed response on the basis of antigenic alteration of kidney parenchymal cells per se; or (3) the presence of residual immunosuppressive agents in the reimplanted kidney.