Role of circulating lipid abnormalities in chronic renal allograft rejection

The evidence that circulating lipid abnormalities may play a role in the pathogenesis of chronic renal allograft rejection is tantalizing but circumstantial. In animal models of cardiac and aorta allograft rejection, lipogenic diets accelerate vascular injury, and treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce vascular injury. Histological studies have demonstrated foam cells and apolipoprotein deposits in the intima of arteries from chronically rejecting human kidneys. Observational studies have found correlations between plasma lipid levels and both acute and chronic rejection. The association between lipid levels and acute rejection in cyclosporine A (CsA)-treated renal transplant recipients suggests the possibility that plasma lipids may influence the immunosuppressive effects of CsA by modulating the lipoprotein-free levels of CsA. If true, such an effect could also explain the result of recent controlled trials showing that HMG-CoA reductase inhibitors reduced graft coronary artery disease and that they prolonged survival in heart transplant recipients. In any case, the hypothesis that circulating lipid abnormalities contribute to chronic renal allograft rejection deserves further testing in well-designed, clinical trials.