Immunosuppressive therapy after kidney transplantation: current and new strategies

Renal transplantation is the treatment of choice for patients with end stage renal disease. The introduction of calcineurin-inhibitors to the immunosuppressive armamentarium was a landmark in the practice of solid organ transplantation, by remarkably decreasing the incidence of acute rejection episodes. Currently, acute rejection occurs in less than 10% of kidney transplant recipients, leading to excellent one-year graft survival. However, long-term graft and patient survival have not followed the same favourable trend. Paradoxically, calcineurin inhibitors themselves contribute to this problem through their nephrotoxic, cardiovascular and oncogenic side-effects. Clinical focus has now shifted to the improvement of long-term outcomes and different therapeutic strategies are being explored for this purpose. The study of calcineurin-inhibitor and corticosteroid sparing treatment protocols constitutes an important field of recent research. The development of pharmacodynamic monitoring tools and pharmacogenetic screening strategies might aid in optimizing the individualization of immunosuppressive therapy. Finally, it is clear that new agents with different mechanisms of action and devoid of the toxicities of current immunosuppressive drugs will be needed as an adjuvant to or replacement of current calcineurin-inhibitor based regimens.