title: [Immunosuppressive treatments: mechanisms of action and clinical use].
abstract: Renal transplantation is the treatment of choice of end stage renal failure. It both improves the quality and the quantity of life compared to other techniques, such as hemodialysis. These results are partly related to the use of immunosuppressive therapy more effective and whose handling has improved over time. Advances in understanding the mechanisms of lymphocyte activation and the phenomena of rejection have in fact better defined the use of these treatments and their associations. Treatments can be broadly classified according to their characteristics (biological or chemical). Among chemical treatments, steroids are widely used, although the question of their avoidance or spearing is still a matter of debate. The cornerstone of immunosuppressive regimens remains the calcineurin inhibitors, characterized by a narrow therapeutic index and the need for therapeutic drug monitoring. Inhibitors of mammalian target of rapamycin (mTOR) have interesting antiproliferative effects that could be important against chronic allograft dysfunction and/or carcinogenesis. However, their safety profile makes them difficult to handle. Inhibitors of purine synthesis are largely based on inhibitors of inosine monophosphate dehydrogenase (IMPDH). Their effectiveness makes them privileged partners of other therapeutic classes. Among biological treatments, it is possible to separate the depleting and non depleting antibodies. Among the former, antithymocyte globulins are mainly active in T cells, whereas rituximab, a monoclonal anti-CD20, is active in B cells involved in the phenomena of humoral rejection. The non depleting antibodies are represented by anti-CD25, directed against the receptor for interleukin-2. In the near future it is likely that the belatacept, a costimulation blockade fusion protein will be used to allow calcineurin inhibitors sparing. Other immunosuppressive agents, acting at different levels of the immune response are being evaluated. In addition, advances in pharmacology offered hope of a better individualization of immunosuppressive therapies and better definition of therapeutic strategies used.
authors.affiliation: Service de transplantation rénale adulte, hôpital Necker-Enfants malades, 149, rue de Sèvres, 75015 Paris, France. eric.thervet@nck.aphp.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Thervet
authors.forename: Julien
authors.initials: J
authors.lastname: Zuber
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sberro
authors.forename: Guillaume
authors.initials: G
authors.lastname: Canaud
authors.forename: Dany
authors.initials: D
authors.lastname: Anglicheau
authors.forename: Renaud
authors.initials: R
authors.lastname: Snanoudj
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Mamzer-Bruneel
authors.forename: Franck
authors.initials: F
authors.lastname: Martinez
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
mesh_terms: D000069594:Abatacept; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D019703:Calcineurin / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007165:Immunosuppression Therapy / Q000379:methods / Q000639:trends; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011788:Quality of Life; D000069283:Rituximab; D020123:Sirolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D065095:Calcineurin Inhibitors; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069283:Rituximab; D000069594:Abatacept; D019703:Calcineurin; D009173:Mycophenolic Acid; D020123:Sirolimus