Campath induction in renal transplantation

Abstract

Kidney transplantation significantly improves quality of life and survival in patients with advanced renal failure and it has become the treatment of choice. Long-term immunosuppressants following transplantation are associated with an increased risk of infection, malignancy and diabetes. Therefore, transplant physicians endeavour to reduce long-term maintenance of the immunosuppression burden and aim to reduce the risk of developing these complications. This has been made possible in the last decade with the introduction of biological induction agents, namely Campath 1H. Campath (Campath-1H) is a humanised rat monoclonal antibody directed against the CD52 antigen, which is one of the most abundant antigens on human lymphocytes. Activation of CD52 antigen causes profound cell lysis and cytokines release. This was thought to be crucial in the mechanism of developing a partial tolerance in transplant recipients. A great interest has developed in its use in transplantation since the first reported use of Campath-1M in solid organ transplantation in the late 1980s and humanised Campath 1H in 1998. Campath had been used as an induction agent together with varying maintenance regimes with different results. In this thesis, I am going to present a brief history of kidney transplantation and a literature review on the use of Campath in transplantation. I will follow by presenting the results and discussions on clinical studies that I developed during my study: the pilot study of Campath induction with tacrolimus monotherapy; CamTac study - a randomised controlled study; the prospective long-term outcomes study; the retrospective cohort dose-finding study; further studies developed to examine the incidence and risk related to long-term immunosuppression – causes of graft loss, long-term allograft pathology, infection, malignancy, haematological profile; and a detailed study on lymphocyte proliferation and rejection following Campath induction.