Statins in solid organ transplantation: is there an immunosuppressive effect?
Cardiac allograft vasculopathy is one of the major causes of mortality late after heart transplantation. This disease process occurs to a lesser extent in patients with other donor organs; however, a long-term graft dysfunction is similarly described in kidney, liver and lung transplant recipients. There are multiple immune and nonimmune risk factors associated with this vasculopathic disease process, one of which includes hyperlipidemia. Use of lipid lowering agents, specifically HMG-CoA reductase inhibitors (statins) was initially reported to have possible immunosuppressive effects in a single center study of heart transplant recipients. This has not been observed in kidney transplant recipients; however, a large randomized trial demonstrated a significant cardiovascular risk reduction in fluvastatin-treated kidney transplant patients, outcome similar to the numerous nontransplant clinical trials of statins in atherosclerosis. In two recent in vitro studies, statins have been reported to repress induction of MHC-II by interferon-gamma and selectively block leukocyte function antigen-1, both of which decrease T-lymphocyte activation. In conclusion, statins appear to have outcome benefits in heart and kidney transplant patients; however, firm evidence for a clinical immunosuppressive effect is lacking. Further studies in humans will be needed to demonstrate this potential effect of statins. Overall, the outcome benefits of statins from the heart and kidney clinical studies provide a firm rationale to support the use of statins in organ transplantation.
Kobashigawa
Jon A
JA
Division of Cardiology, UCLA Medical Center, Los Angeles, CA 90095, USA. jonk@mednet.ucla.edu
D001161:Arteriosclerosis / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D002986:Clinical Trials as Topic; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D016030:Kidney Transplantation; D050356:Lipid Metabolism; D008285:Major Histocompatibility Complex; D016377:Organ Transplantation / Q000379:methods*; D019172:Transplantation Conditioning
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D002784:Cholesterol