Effect of sirolimus on carotid atherosclerosis in kidney transplant recipients: data derived from a prospective randomized controlled trial

Abstract

Background. In animal models, the mammalian target of rapamycin inhibitors (mTORIs) may prevent atherogenesis by the regulation of homeostasis of cholesterol and by a reduced inflammatory response. The aim of this study is to compare the carotid intima-media thickness (cIMT) between de novo tacrolimus/mycophenolate and tacrolimus/sirolimus at low doses. The cIMT is considered a surrogate marker of atherosclerosis. Methods. We evaluated cIMT at baseline and at 6 and 12months after kidney transplantation in a database derived from a previously published trial. That trial had prospectively randomly assigned kidney transplant recipients older than 60 years of age to one of two groups: tacrolimus/sirolimus (n = 21) or tacrolimus/mycophenolate (n = 23). The cIMT was evaluated by using ultrasound in the common carotid artery wall on both sides. Results. The total and high-density lipoprotein cholesterol levels were higher in the sirolimus group at 6 and 12 months. The cIMT decreased over time at 6 and 12 months in the sirolimus group (P = 0.012); this decrease continued to be significant in a model adjusted for age, sex, presence of diabetes, statin use and smoking. Conclusions. The use of sirolimus plus tacrolimus de novo in kidney transplantation is associated with a reduction in cIMT after 12 months, a decrease more significant than seen with the combination of mycophenolate plus tacrolimus. This suggests a class effect of mTORI in the prevention of atherosclerosis.