The effects of lipid-lowering agents on acute renal allograft rejection

Background. Preliminary results from clinical trials suggest that 3-hydroxy -3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute r enal allograft rejection. However, the mechanism for this putative effect o f 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown. Methods. Immediately after renal transplantation we randomly allocated (pro portioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvasta tin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52). Results. Simvastatin, but not gemfibrozil, reduced total and low density li poprotein cholesterol during the first 90 days posttransplant. There were n o major adverse effects of therapy. However, there were no effects of treat ment on acute rejection. Indeed, survival free of acute rejection at 90 day s was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% i n the placebo control group (P=0.771). A post hoe power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acut e rejection (versus placebo) was not detected, and a 2.5% chance that an ef fect of gemfibrozil on acute rejection (versus placebo) was not detected in this study. Conclusion. Lipid-lowering agents may not reduce the incidence of acute ren al allograft rejection. However, additional studies are needed to confirm t his observation. In the mean time, many if not most renal transplant recipi ents should be treated with HMG-CoA reductase inhibitors starting early pos ttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.