Which of the following drugs is most likely to cause nephrotoxicity when used in combination with another calcineurin inhibitor?

Tacrolimus is a potent immunosuppressant that belongs to the class of calcineurin inhibitors, often used in organ transplantation to prevent rejection. When used in combination with another calcineurin inhibitor, it can significantly increase the risk of nephrotoxicity. This is because both drugs work through similar pathways, resulting in cumulative effects that raise the chances of renal impairment, particularly affecting kidney function by causing vasoconstriction of the renal blood vessels and potentially leading to acute kidney injury.

The other options, while they may have their own side effects, do not pose the same level of nephrotoxic risk when paired with another calcineurin inhibitor. Prednisone, for instance, is a corticosteroid that typically does not have the same nephrotoxic potential, and mycophenolate mofetil, an antimetabolite, primarily affects the proliferation of lymphocytes rather than directly causing kidney damage. Cytokine inhibitors, depending on their specific mechanism, also do not share the nephrotoxic risks seen with calcineurin inhibitors. Thus, the combination of tacrolimus with another calcineurin inhibitor is the most concerning regarding nephrotoxicity, making it the correct choice.