Transplant Immunosuppression: Calcineurin Inhibitors – Cyclosporine and Tacrolimus

Cyclosporine and tacrolimus are calcineurin inhibitors. After a T lymphocyte recognizes foreign graft tissue, calcineurin normally enables transcription of interleukin-2, a signal that supports T-cell activation and expansion. Blocking calcineurin reduces interleukin-2 transcription, dampens the cellular immune response, and lowers the chance of graft rejection. That same immune suppression creates the central trade-off: the graft is protected, but the patient is less able to control infection and abnormal lymphocyte proliferation. The indications are product-specific. Current Canadian PROGRAF information lists prevention of rejection after allogeneic liver, kidney or heart transplantation and treatment of refractory rejection after liver or kidney transplantation. Do not transfer every cyclosporine indication or every off-label calcineurin-inhibitor use to tacrolimus as though all products share identical authorization. In Canada, cyclosporine also has approved use for severe psoriasis, and tacrolimus has an approved use for rheumatoid arthritis. A kidney-transplant recipient with a new creatinine rise illustrates why the mechanism alone is not enough. The change may reflect calcineurin-inhibitor nephrotoxicity, rejection, dehydration, infection, obstruction, or an interacting medication that has raised the drug concentration. Assess the patient and notify the...