Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus

Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In study 1, the effects of immuno suppress ants, cyclosporine (CsA) and tacrolimus on serum lipids we re compared in-patients undergoing renal transplantation. The study include d 32 cases of renal transplantation recipients who randomized to the CsA tr eatment group (15 patients) and the tacrolimus group (17 patients). Before and 1 month after the transplantation, we assessed the serum lipid levels, apolipoprotein levels, the concentrations of cholesterol in the respective lipoprotein fractions and the enzyme activities related to lipid-metabolism . The serum lipid levels in both groups were significantly increased at 1 m onth after renal transplantation. In the CsA group, there were significant increases in cholesterol contents in very-low-density lipoprotein (VLDL), L DL2 and HDL2 fractions, whereas, in the tacrolimus group, cholesterol conte nt was increased in VLDL and HDL2 fractions. In study 2, 1 month after rena l transplantation, 19 patients with hypercholesterolemia (total cholesterol (TC) > 200 mg/dl) and hypertriglyceridemia (triglyceride (TG) > 150 mg/dl) were treated with simvastatin 5-10 mg/day for 6 months. Sinavastatin treat ment significantly decreased serum TC (240 +/- 29-200 +/- 22 mg/dl, P < 0.0 01), low-density lipoprotein cholesterol (LDL-C; 114 +/- 20-99 +/- 17 mg/dl , P < 0.05) and TG levels (217 +/- 103-130 +/- 38 mg/dl, P < 0.01). In addi tion, there were significant decreases in very-low-density lipoprotein chol esterol (VLDL-C; 53 +/- 20-34 +/- 15 mg/dl, P < 0.001). The Cmax and AUC of simvastatin were increased about eight-fold, when simvastatin was given in combination with CsA. In contrast, no significant changes in simvastatin l evels were observed when combination with tacrolimus. Although simvastatin levels were increased with CsA, there were no abnormal changes in renal and liver functions, creatinine phosphokinase (CPK) levels or in incidence of adverse effects. (C) 2001 Elsevier Science Ireland Ltd, All rights reserved .