Non-Phased Study of the Use of a Single Dose of Thymoglobulin for Immunosuppressive Induction in Renal Transplant Recipients as Compared to a Standard Four Dose Regimen

Induction therapy, using polyclonal or monoclonal antibody preparations as an adjunct immunosuppressive agent during the initial transplant period, has helped to decrease the incidence of acute rejection significantly. In the 1980's acute rejection occurred in approximately 50% of renal transplant recipients. In the current era of transplantation, the combination of potent induction agents and newly available maintenance immunosuppressive agents has reduced the acute rejection rate to less than 20% at most transplant centers. Our center has routinely achieved acute rejection rates of approximately 5% using a standard induction protocol with the polyclonal antibody agent Thymoglobulin.

Preventing acute rejection significantly decreases the requirement for re-hospitalization, the need for diagnostic renal allograft biopsy and subsequent exposure to high dose corticosteroids and other immunosuppressive agents. The threat of early allograft loss secondary to rejection refractory to treatment or permanent injury and shortened graft survival following treatment of a severe rejection is also circumvented.

Polyclonal antibody preparations are produced by immunizing animals with human lymphocytes or thymocytes. Polyclonal antibody preparations are approved for treatment of acute renal allograft rejection, but are routinely used as induction agents and for prevention of rejection in all solid organ allografts. Commercially available preparations in the United States are equine/thymocyte derived (Atgam, Pharmacia & Upjohn, Kalamazoo, MI) and rabbit/thymocyte derived (Thymoglobulin, Genzyme, Cambridge, MA).

Rabbit derived preparations are thought to be potentially more efficacious than equine derived products. Studies performed at this renal transplant center demonstrated that Thymoglobulin has superior efficacy compared to Atgam in the prevention of rejection (1). Not only was the acute rejection rate lower, but graft survival was also better at 1 and 5-years (1). [Hardinger, 2004 #18]. This result has been attributed in part to a more pronounced and prolonged lymphopenia induced by Thymoglobulin (2).

The broad specificity of polyclonal agents to multiple cell signaling and adhesion molecules provides a theoretic advantage compared to monoclonal antibodies. In addition to inducing a profound and prolonged lymphopenia through complement-dependent lysis or by opsonization and phagocytosis, the broad specificity of polyclonal antibody agents affects multiple costimulatory and adhesion molecules involved in cellular and antibody mediated immune processes. The effects on adhesion molecules, cytokines, chemokines and platelets may be critical to the noted decrease in the incidence of delayed renal allograft function associated with initiation of Thymoglobulin therapy intraoperatively (3). Prevention of delayed graft function may also subsequently decrease the incidence of acute rejection and prolong allograft survival.