What is the role of calcineurin inhibitor-free regimens for immunosuppression after solid organ transplantation?

Updated: Jan 04, 2016
  • Author: Bethany Pellegrino, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Because of the risk of both acute and chronic nephrotoxicity attributed to calcineurin inhibitors, the development of protocols free of these agents is desirable. [12] The use of sirolimus, mycophenolate mofetil, and anti-CD25 antibodies has been studied to determine whether graft survival and acute rejection rates can be maintained at the present rates in the absence of a calcineurin inhibitor.

The withdrawal of cyclosporine has been investigated in several trials. While the long-term graft survival rates were similar in patients withdrawing from cyclosporine compared with those maintained on it, the incidence of acute rejection in the withdrawal group was higher. The addition of sirolimus has been used in these withdrawal protocols, with a suggestion of improved renal function at 2-year follow-up. Higher rates of acute rejection were again noted in the withdrawal group.

Many other protocols that minimize exposure to calcineurin inhibitors have been studied. Promising protocols include sirolimus, mycophenolate mofetil, and steroids or the combination of anti-CD25 antibodies, sirolimus, mycophenolate mofetil, and steroids. One study has shown that belatacept plus mycophenolate mofetil or belatacept plus sirolimus provide primary immunosuppression with acceptable rates of acute rejection, improved renal function compared to a TAC-based regimen, and may avoid the need for calcineurin inhibitors and corticosteroids. [13] These protocols have shown acceptable graft survival rates and acute rejection rates, although the studies are small and further research is warranted. In short, multiple regimens have been shown to be effective.

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