title: [Use of new non-nephrotoxic immunosuppressive drugs in kidney transplantation, especially after ischemia-reperfusion injury].
abstract: Medium- and long-term renal graft survival depends on 4 main factors: the quality of the harvested graft, ischemia-reperfusion injury during harvesting and re-implantation, rejection, and the nephrotoxicity of certain drugs (especially immunosuppressants) used in this setting. The most nephrotoxic immunosuppressive drugs are the anticalcineurins (cyclosporine A and tacrolimus), a class discovered in the late 1970s and currently representing a basic component of all immunosuppressive protocols for solid organ graft recipients. The renal tubular and vascular toxicity of anticalcineurins is due to their immunosuppressive mechanism: they block the calcineurin pathway and thereby prevent transmission of the first signal from the T cell receptor to the nucleus, which normally triggers cytokine synthesis, New non-nephrotoxic immunosuppressants are therefore needed, especially for grafts of poor quality or subject to severe ischemia-reperfusion injury. Attention is turning to "old " molecules such as anti-thymocyte globulins, but exciting new immunosuppressants are now appearing. Alefacept is a fusion protein that binds to the immunological synapse-associated molecule CD2, which normally interacts with LFA-3. Belatacept, another fusion protein, blocks the T cell second signal CD 28-B7.1/B7.2. Finally, new chemical agents are being developed, such as sautrasporine, a tyrosine kinase inhibitor, and tofacitinib, a Jak inhibitor.
authors.affiliation: Néphrologie, CHU de Bicêtre 94275 Kremlin Bicêtre Cedex et Unité Mixte de Recherche 1014 INSERM/Universitê Paris-Sud 11, Hôpital Paul Brousse 94800 Villejuif. bernard.charpentier@bct
authors.forename: Bernard
authors.initials: B
authors.lastname: Charpentier
authors.forename: Séverine
authors.initials: S
authors.lastname: Beaudreuil
authors.forename: Hélène
authors.initials: H
authors.lastname: Francois
authors.forename: Antoine
authors.initials: A
authors.lastname: Jacquet
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
mesh_terms: D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D015427:Reperfusion Injury / Q000517:prevention & control; D014181:Transplantation Immunology
chemical_list: D007166:Immunosuppressive Agents