The last decade has witnessed two main shifts in the interests of the transplant community: long-term renal transplant outcome and crossing the HLA and ABO barriers. Three new paradigms have therefore emerged as a direct result of these interests: individualization and minimization aiming at improving long-term outcome; and desensitization aiming at expanding the donor pool.
Individualization and minimization stem from the delicate balance between under immunosuppression leading to graft rejection, and over immunosuppression leading to cardiovascular disease (CVD), infection, malignancy, and/or nephrotoxicity. These factors, especially CVD, have been clearly linked to poor long-term outcome. Individualization strategies are currently based on generalized perception of immunologic risks or on expected or existing drug toxicities. For example, patients perceived to be at high risk for allograft rejection receive more immunosuppression (induction and maintenance) as compared with those who are perceived to be at low risk for allograft rejection (maintenance only). Minimization strategies are based on minimizing immunosuppressive drug toxicities with special emphasis on reducing nephrotoxicity and other direct cardiovascular side effects of currently used agents. Individualization and minimization should not be used synonymously, as patients at high risk for immunologic graft losses for example require maximal immunosuppression as part of their individualization. On the other hand, minimization strategies are usually reserved for low risk patients (individualization of the minimization).
Desensitization is based on abrogating a positive crossmatch with the intended donor (living or deceased) therefore rendering kidney transplantation possible. A new phase of immunosuppression (preconditioning) was therefore added to the established induction and maintenance phases of immunosuppression.
Future directions in the tailoring of immunosuppression will be based on comprehensive immune monitoring of the recipient to determine whether the patient is receiving minimum, maximum or adequate immunosuppression.