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Advances in immunosuppression for renal transplantation

Abstract

The development of immunosuppressants with minimal adverse and nephrotoxic effects is important to improve outcomes, such as acute and chronic antibody-mediated rejection, after organ transplantation. In addition, the application of expanded criteria for donors and transplantation in immunized patients necessitates the development of new therapies. Drug development over the past 10 years has generally been disappointing, but several new promising compounds have been or are being developed to prevent acute and chronic transplant rejection. In this Review, we report on several compounds that have been developed to remove allogenic T cells and/or to inhibit T-cell activation. We also discuss compounds that interfere with antibody-mediated rejection.

Key Points

  • Allogenic organ transplantation is limited by drug-associated toxicity and the occurrence of antibody-mediated or chronic rejection

  • Improved understanding of the molecular mechanisms of rejection has led to the development of agents that regulate T-cell function, complement activation and/or the survival of plasma and B cells in immunized or naive patients

  • These new agents may control acute, antibody-mediated rejection and chronic rejection to increase long-term renal transplantation outcomes

  • The safety of these new agents remains to be evaluated to ensure that they do not increase the risk of infections or tumor formation in transplanted patients

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Figure 1: Intracellular signaling and inhibition by novel compounds.

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Acknowledgements

The authors thank Professor Lionel Rostaing (Head of the Department of Transplantation, Rangueil Teaching Hospital, Toulouse, France) for his constructive discussion and advice.

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Correspondence to Bernard Charpentier.

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Durrbach, A., Francois, H., Beaudreuil, S. et al. Advances in immunosuppression for renal transplantation. Nat Rev Nephrol 6, 160–167 (2010). https://doi.org/10.1038/nrneph.2009.233

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