Alloantibody and renal transplantation.

With the introduction of the immunosuppressive drug Cyclosporin A (CyA) into clinical practice, renal transplantation has become a safer and more successful therapy for end stage renal failure. Rejection by both humoral and cellular mechanisms remains the main cause of graft failure. The allosensitised patient is at greater risk from early rejection episodes that are difficult to treat. Patients become allosensitised through exposure to alloantigen by organ transplantation, pregnancy, and blood transfusion. The detection of alloantibody by a complement mediated lymphocytotoxicity test is widely used as a measure of allosensitisation. The first part of this study is a detailed review of the Leicester experience with CyA and the management of the allosensitised patient. This confirms a relationship between allosensitisation as detected by alloantibody and renal allograft rejection resistant to treatment. Nevertheless, using current methods 50% of allosensitised patients were transplanted without early rejection episodes. The second part of the study describes a new model of accelerated renal allograft rejection by allosensitised dogs, where recipients receive a kidney across a positive lymphocytotoxic crossmatch. CyA is of no benefit in delaying rejection by these allosensitised recipients, except when the lymphocytotoxic crossmatch test is negative. Two other strategies were unsuccessful in the face of a positive lymphocytotoxic crossmatch test: the use of cyclophosphamide and cytosine arabinoside to immunomodulate the allosensitised recipient prior to transplantation, and prostacyclin given in conjunction with CyA after renal transplantation. This experimental model may be of use in the further study of the clinical problem posed by the allosensitised patient.