DUAL ROLES OF HMG-COA REDUCTASE INHIBITORS IN SOLID-ORGAN TRANSPLANTATION - LIPID-LOWERING AND IMMUNOSUPPRESSION

Hyperlipidemia has been associated with the development of transplant coronary vasculopathy (TCV) in heart transplant recipients and chronic rejection in kidney transplant recipients. HMG-CoA reductase inhibito rs (HMGCoARIs) are effective in treating post-transplant hyperlipidemi a, but their effects on patient and graft outcome remain unclear. In a prospective randomized trial investigating pravastatin (PVS) use earl y after heart transplantation, we observed that PVS treated patients h ad a decreased incidence of clinically severe acute rejection episodes resulting in a significant improvement in one year survival (94% vs. 78% in the control group, P = 0.02), and decreases in both the inciden ce and progression of TCV. This observation was validated in a prospec tive randomized study of kidney transplant recipients where we found t hat PVS reduced the incidence of acute rejection episodes (25% vs. 58% in the control group, P = 0.01). In both the heart and kidney transpl ant recipients taking PVS, we noted decreases in natural killer cell ( NKC) cytotoxicity. In vitro studies reveal that: PVS inhibits NKC cyto toxicty; PVS acts synergistically with cyclosporine to inhibit cytotox ic lymphocyte activity; and, other HMGCoARIs inhibit T-cell proliferat ion and monocyte chemotaxis. In conclusion, HMGCoARIs may have immunos uppressive properties in transplant recipients that could be useful in combating acute and chronic rejection.