Which of the following immunosuppressive drugs is MOST likely to cause renal dysfunction?
- □ (A) Tacrolimus
- □ (B) Mycophenolate mofetil
- □ (C) Basiliximab
Immunosuppressant drugs are used to prevent or treat allograft rejection. Most of these drugs act during the induction phase of the immunological response, reducing lymphocyte proliferation. Some of them are also used in the maintenance phase. There are three main groups based on the site of action: interleukin-2 (IL-2) production or action, cytokine gene expression, or purine or pyrimidine synthesis. Complications of chronic immune suppression drugs are shown in the Table.
Tacrolimus is a macrolide antibiotic with an action very similar to that of cyclosporine. However, it is more potent and has a shorter half-life. It blocks the action of calcineurin, leading to reduction in various transcription factors and IL-2 expression, primarily in T-helper lymphocytes. Tacrolimus can lead to renal toxicity due to afferent arteriolar vasoconstriction and the subsequent reduction in glomerular filtration rate (GFR). Decreasing the dose of tacrolimus can reverse GFR reduction and renal toxicity. Tacrolimus therapy has also been associated with hypertension and neurotoxicity.
Mycophenolate mofetil restrains the proliferation of both T and B cells by inhibiting de novo purine synthesis in these cells. It may be associated with adverse gastrointestinal effects, but it is not as likely as tacrolimus to cause renal dysfunction.
Basiliximab is a chimeric monoclonal antibody to CD25 and an IL-2 antagonist. It is used as an alternative or in addition to steroids for the induction of immunosuppression in solid organ transplantation. It has a relatively safe profile. No cytokine release syndrome has been associated with this drug, but anaphylactic reactions can occur. Basiliximab is unlikely to cause renal dysfunction.