New immunosuppressive strategies in renal transplant recipients.
Along with expanded knowledge of pathophysiological processes involved in transplant rejection, a variety of immunosuppressive agents with very specific modes of action have been developed. The focus of this review is an update on the pathophysiologic rationale and experience with such agents in human renal transplantation that are currently clinically available or are under investigation in human trials. Clinical data are reviewed with respect to calcineurin inhibitor sparing regimens based on mycophenolate or sirolimus, the use of leflunomide and its derivative FK778, modulation of chemotaxis with FTY720 or chemokine receptor blockers and the results of costimulatory blockade. While selection of one of these strategies may allow a more individualised therapy, the immunosuppressive potential of each compound has to be weighed against adverse reactions for an individual patient.
Fischereder
Michael
M
Nephrology Center, Medizinische Poliklinik Innenstadt, Ludwig-Maximilians University, Munich, Germany. Michael.Fischereder@medpoli.med.uni-muenchen.de
Kretzler
Matthias
M
D000480:Alkynes; D000818:Animals; D018925:Chemokines / Q000037:antagonists & inhibitors; D002633:Chemotaxis / Q000187:drug effects; D000068338:Everolimus; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007555:Isoxazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016030:Kidney Transplantation; D000077339:Leflunomide; D008213:Lymphocyte Activation / Q000187:drug effects; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D022061:Tacrolimus Binding Protein 1A / Q000037:antagonists & inhibitors
D000480:Alkynes; D018925:Chemokines; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D009570:Nitriles; D047428:Protein Kinase Inhibitors; C115284:2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D022061:Tacrolimus Binding Protein 1A; D000077339:Leflunomide; D009173:Mycophenolic Acid; D020123:Sirolimus