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Novel immunosuppressive agents in kidney transplantation

World Journal of Transplantation 2013年第4期3卷 68-77页

作者： Karen L Hardinger Daniel C Brennan Department of Pharmacy Practice and Administration University of Missouri-Kansas CityKansas CityMO 64108United States Department of Medicine Washington University School of Medicine in St. LouisSt. LouisMO 63110United States

Excellent outcomes have been achieved in the field of renal transplantation. A significant reduction in acute rejection has been attained at many renal transplant centers using contemporary immunosuppressive, consisting of an induction agent, a calcineurin inhibitor, an antiproliferative agent plus or minus a corticosteroid. Despite improvements with these regimens, chronic allograft injury and adverse events still persist. The perfect immunosuppressive regimen would limit or eliminate calcineurin inhibitors and/or corticosteroid toxicity while providing enhanced allograft outcomes. Potential improvements to the calcineurin inhibitor class include a prolonged release tacrolimus formulation and voclosporin, a cyclosporine analog. Belatacept has shown promise as an agent to replace calcineurin inhibitors. A novel, fully-human anti-CD40 monoclonal antibody, ASKP1240, is currently enrolling patients in phase 2 trials with calcineurin minimization and avoidance regimens. Another future goal of transplant immunosuppression is effective and safe treatment of allograft rejection. Novel treatments for antibody mediated rejection include bortezomib and eculizumab. Several investigational agents are no longer being pursed in transplantation including the induction agents, efalizumab and alefacept, and maintenance agents, sotrastaurin and tofacitinib. The purpose of this review is to consolidate the published evidence of the effectiveness and safety of investigational immunosuppressive agents in renal transplant recipients.

关键词： Review Immunosuppression Investigational agents renal/kidney transplant

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Current state of renal transplant immunosuppression:Present and future

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World Journal of Transplantation 2012年第4期2卷 51-68页

作者： Hari Varun Kalluri Karen L Hardinger Department of Pharmaceutical Sciences School of PharmacyUniversity of PittsburghPittsburghPA 15260United States Karen L Hardinger Department of Pharmacy Practice and AdministrationUniversity of Missouri-Kansas CityKansasMO 64108United States

For kidney transplant recipients, immunosuppression commonly consists of combination treatment with a calcineurin inhibitor, an antiproliferative agent and a corticosteroid. Many medical centers use a sequential immunosuppression regimen where an induction agent, either an anti-thymocyte globulin or interleukin-2 receptor antibody, is given at the time of transplantation to prevent early acute rejection which is then followed by a triple immunosuppressive maintenance regimen. Very low rejection rates have been achieved at many transplant centers using combinations of these agents in a variety of protocols. Yet, a large number of recipients suffer chronic allograft injury and adverse events associated with drug therapy. Regimens designed to limit or eliminate calcineurin inhibitors and/or corticosteroid use are actively being pursued. An ideal immunosuppressive regimen limits toxicity and prolongs the functional life of the graft. This article contains a critical analysis of clinical data on currently available immuno-suppressive strategies and an overview of therapeutic moieties in development.

关键词： Review Immunosuppression Investigational agents renal/kidney transplant

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