Monoclonal Antibodies Administered at the Time of Transplant
Current maintenance immunosuppression is aimed at various targets within the immune system to halt propagation of signal transduction pathway. Available agents, although effective, are associated with sig-nificant patient and allograft adverse effects which are associated with long-term exposure (Table 3). The leading cause of death in non-cardiac transplant recipients is a cardiovascular event. These cardiovas-cular events have been linked to long-term corticos-teroid exposure. In addition, chronic administration of calcineurin inhibitors (cyclosporine and tacrolimus) is also associated with acute and chronic kidney dysfunction leading to hemodialysis or need for a kidney transplant. Monoclonal antibodies given at the time of transplant (induction) have been used to decrease the need for corticosteroids and allow for the delay or a reduction in the amount of calcineurin inhibitor used. Determination of the solid organ transplant recipient’s immunologic risk at the time of transplant is necessary to determine which mono-clonal antibody to use in order to minimize the risk of early acute rejection and graft loss. Recipients are stratified based on several donor, allograft and recipient variables to determine their immunologic risk. Patients at high risk for acute rejection or those in
which maintenance immunosuppression is going to be minimized should receive a polyclonal or mono-clonal antibody that provides cellular apoptosis, for example alemtuzumab or rabbit-antithymocyte glo-bulin. Recipients at low risk for acute rejection may receive a monoclonal antibody which provides im-munomodulation without lymphocyte depletion, such as basiliximab or daclizumab.
Several important pharmacokinetic parameters must be considered when these agents are adminis-tered to the various organ transplant recipients. The volume of distribution, biological half-life and total body clearance can differ significantly from a kidney transplant recipient to a heart transplant recipient. Clinicians must consider when to administer mono-clonal antibodies in different transplant populations to maximize efficacy and minimize toxicity. For example, heart and liver transplant recipients tend to lose large volumes of blood around the time of transplant, therefore intraoperative administration may not be the optimal time to administer a monoclonal antibody since a large portion may be lost during surgery. Monoclonal antibodies are also removed by plasma exchange procedures, such as plasmapheresis, which may be performed during the perioperative period (Nojima et al., 2005).