Calcineurin inhibitors (CNIs) have been the primary immunosuppressive agents employed in solid organ transplantation since the early 1980s, with ciclosporin A and tacrolimus improving both short-term and long-term survival rates. Many current immunosuppressive regimens which use tacrolimus in combination with mycophenolate mofetil and corticosteroids have improved graft and patient survival, with one-year graft survival rates of 80−95% being achieved (Kern and Sucher, 2012).
Both ciclosporin A and tacrolimus inhibit T cell activation and proliferation by interference with the interleukin 2 (IL-2) pathway (Kern and Sucher, 2012).
However, both ciclosporin A and tacrolimus have significant adverse effects, being associated with nephrotoxicity, and chronic kidney and vascular damage. Current regimens aim to reduce or eliminate the dose of CNIs in solid organ transplantation (Flechner et al., 2008; Casey and Meier-Kriesche, 2011).
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