Effect of fluvastatin on acute renal allograft rejection: A randomized multicenter trial

Background. Statin therapy has been reported to reduce the acute rejection rate following renal transplantation in a pilot study. The present study is the first randomized, double-blind and adequately powered study to examine the effect of statins on acute rejection of renal allografts. Methods. A total of 364 patients were randomly assigned to receive either f luvastatin 40 mg or placebo in combination with conventional cyclosporine-b ased immunosuppressive therapy. The primary end point was treated first acu te rejection. Secondary end points included biopsy-proven rejection, histol ogical severity of rejection, occurrence of steroid-resistant rejection, an d serum creatinine at three months following transplantation. Results. Fluvastatin was well tolerated; no patients developed myositis or rhabdomyolysis. There was no difference in the acute rejection rate [86 (47 .3%) fluvastatin vs. 87 (47.8%) placebo] and no significant difference in t he severity of rejection, steroid resistant rejection or mean serum creatin ine at three months (160 mu mol/L vs. 160 mu mol/L). Total cholesterol, low -density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol a nd triglyceride levels increased following renal transplantation. With the exception of the increase in HDL-C, which was augmented, the increases in l ipid parameters were significantly reduced by fluvastatin (total cholestero l +17.5% vs. 35.7%; LDL-C +6.3% vs. 46.7%; HDL-C +43.3% vs. 38.1%; triglyce ride +52.2% vs 77.6%). Conclusions. Contrary to the reported effects of statins, fluvastatin had n o effect on the incidence or severity of acute rejection following renal tr ansplantation. There were no increases in adverse events. A significant and potentially beneficial alteration in the lipid profile was observed in the early post transplant period. We conclude that fluvastatin may be used saf ely to correct dyslipidemia in patients with end-stage renal failure throug h the peri-transplant period.