What is the role of cyclosporine in immunosuppression after pediatric transplantation?

Updated: Oct 18, 2019
  • Author: Randy P Prescilla, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Answer

Answer

Cyclosporine (Sandimmune, Neoral)

Cyclosporine (CsA) was derived from the fungus Tolypocladium inflatum Gams and has been approved as a primary immunosuppressant for more than 2 decades.

The complex of CsA and cyclophilin is now known to inhibit the phosphatase activity of calcineurin. By preventing calcineurin-mediated dephosphorylation, CsA inhibits translocation of the nuclear factor of activated T cells (NFAT) family of transcription factors from the cytoplasm to the nucleus of activated T cells. In addition, CsA blocks the JNK and p38 signaling pathways that are triggered by antigen recognition in T cells.

Adverse effects of CsA include nephrotoxicity, systemic hypertension, gingival hyperplasia, and neurotoxicity. A possible role in promoting cancer progression and tumor cell invasion and metastasis has been raised.

A retrospective study of 141 kidney transplant recipients compared the results of those treated with or without CsA. The findings of the 3-month, 24-month, and 10-year protocol biopsies suggest that although histological lesions are commonly attributed to CsA nephrotoxicity, they were not specific enough to definitively diagnose calcineurin inhibitor nephrotoxicity. [5]


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