Beyond calcineurin inhibitors: emerging agents in kidney transplantation

Despite their effectiveness, calcineurin inhibitors (CNIs) represent a major obstacle in the improvement of long-term graft survival in transplantation. The identification of new agents to implement CNI-free regimens is the focus of current transplant research. The purpose of this review is to summarize the novel immunosuppressive agents, including details about their mechanisms of action, stages of development, potential benefits and challenges.

Targeting costimulation with belatacept is now an option for controlling the alloimmune response and has proved to be more effective in preserving long-term allograft function than CNIs despite an increased rate of acute rejection in some studies. mTOR inhibitors are also promising with their remarkable antineoplastic properties, though frequent side-effects may limit their broader use. Other agents under development include JAK inhibitors, CD40 blockade and leukocyte adhesion blockers, with unique potential benefits and side-effects in transplantation.

Novel immunosuppressive agents are now available for use in CNI-free regimens in solid organ transplantation. Timing of initiation as well as long-term efficacy and safety are questions that remain to be answered in future clinical trials.