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

Andre L Silva1, Daniéliso R Fusco1, Hong S Nga1

  • 1Department of Internal Medicine-UNESP, Univ Estadual Paulista, Botucatu, Brazil.

Clinical Kidney Journal
|December 8, 2018
PubMed
Abstract

Insights

Sirolimus combined with tacrolimus in kidney transplant patients significantly reduced carotid intima-media thickness, a marker of atherosclerosis. This suggests mammalian target of rapamycin inhibitors (mTORIs) may prevent atherosclerosis progression.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Mammalian target of rapamycin inhibitors (mTORIs) show potential in preventing atherosclerosis in animal models.
  • mTORIs may regulate cholesterol homeostasis and reduce inflammation, key factors in atherogenesis.
  • Carotid intima-media thickness (cIMT) is a validated surrogate marker for atherosclerosis.

Purpose of the Study:

  • To compare the effect of de novo tacrolimus/mycophenolate versus tacrolimus/sirolimus on cIMT in kidney transplant recipients.
  • To evaluate the role of low-dose mTOR inhibitors in preventing atherosclerosis post-transplantation.

Main Methods:

  • A retrospective analysis of a randomized trial database involving kidney transplant recipients over 60 years old.
  • Patients were assigned to either tacrolimus/sirolimus (n=21) or tacrolimus/mycophenolate (n=23) groups.
  • cIMT was assessed using ultrasound of the common carotid artery at baseline, 6, and 12 months post-transplantation.

Main Results:

  • The sirolimus group exhibited higher total and high-density lipoprotein cholesterol levels at 6 and 12 months.
  • A significant decrease in cIMT was observed in the sirolimus group at 6 and 12 months (P=0.012).
  • This cIMT reduction remained significant after adjusting for age, sex, diabetes, statin use, and smoking.

Conclusions:

  • De novo sirolimus plus tacrolimus therapy in kidney transplant recipients is associated with a significant reduction in cIMT after 12 months.
  • The observed decrease in cIMT was more pronounced compared to the mycophenolate plus tacrolimus combination.
  • These findings suggest a potential class effect of mTOR inhibitors in the prevention of atherosclerosis.
Keywords:
atherosclerosiscarotid intima–media thicknesskidney transplantationmammalian target of rapamycin inhibitorssirolimus

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