Current concepts and perspectives of immunosuppression in organ transplantation
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While early surgical success made organ transplantation possible in the 1950s and 1960s, the breakthrough in clinical organ transplantation was achieved through the discovery and invention of modern immunosuppressive agents in the early/mid-1980s. Especially during the 1990s, a large array of immunosuppressants has expanded the armamentarium used to prevent and treat allograft rejection, resulting in an excellent short-term and an acceptable long-term outcome. However, these drugs have potent but still non-specific immunosuppressive properties and frequently show severe acute and chronic side effects, sometimes questioning the overall success.
As the “Holy-Grail” of the transplant community, the induction of “true donor-specific tolerance” has not been achieved yet; current immunosuppressive strategies, in particular in Europe, include “individually tailored immunosuppressive” protocols, mostly based on specific immunologic and non-immunologic risk factors. These protocols allow for optimal immunosuppressive protocols for each patient group according to their needs by choosing the most suitable, well-tolerated combination of agents and the most effective doses to avoid acute rejection episodes (incidence and severity) and minimise drug-related toxicity to reduce long-term drug-related morbidity and mortality. Nevertheless, transplant recipient are still being forced to take a life-long course of chemical immunosuppressive agents to keep their graft, knowing about the possible life-threatening side effects.
We review current trends of immunosuppressive protocols in liver and kidney transplantation, focusing on calcineurin-inhibitor-sparing protocols, mammalian-target-of-rapamycin (mTOR) inhibitor based-protocols and corticosteroid-avoidance protocols, being aware of the fact, that most of these strategies could be applicable for other transplanted organs, too. Finally, we describe future trends and new developments that are rising on the horizon.