In an effort to reduce the long-term toxicities of immunosuppressant drugs, corticosteroid
and calcineurin inhibitor-sparing immunosuppression protocols have become increasingly popular in
managing kidney transplant recipients. The use of induction antibody therapy and potent residual
immunosuppressants have increased the safety of steroid-free regimens, resulting in a paradigm shift
towards earlier elimination of steroids after kidney transplantation. However, even in the modern era,
results of randomized trials generally indicate that steroid elimination increases the risk of rejection
compared to maintenance steroid therapy. Among calcineurin inhibitor-sparing strategies, withdrawal
of these agents after their initial use in stable patients, or conversion to either mycophenolate mofetil or
sirolimus in patients with renal dysfunction appears to yield the greatest benefit in preserving renal
function. The outcomes of calcineurin inhibitor avoidance protocols have been mixed but have fallen
into disfavor. The benefits of minimizing immunosuppression in kidney transplant recipients must be
weighed against the risks of precipitating acute rejection or chronic allograft dysfunction. Additional
research is needed to identify clinical and immune parameters that will enable selection of patients for
whom the benefits outweigh the risks. In addition, the transplant community is in need of newer agents
that can potently prevent rejection without the need for corticosteroids or calcineurin inhibitors.
Keywords: Immunosuppression, Corticosteroids, Calcineurin Inhibitors, Tacrolimus, Cyclosporine,
Sirolimus, Everolimus, Calcineurin-Free Protocols, Tolerance, Mycophenolate Mofetil.
