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LDL S-homocysteinylation decrease in chronic kidney disease patients undergone lipid lowering therapy

Angelo Zinellu1, Salvatore Sotgia, Elisabetta Pisanu

  • 1Department of Biomedical Sciences, University of Sassari, Italy. azinellu@uniss.it

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|June 5, 2012
PubMed

Insights

Lipid-lowering therapy in chronic kidney disease (CKD) patients reduced low molecular weight (LMW) thiols bound to LDL. Combined therapy with higher simvastatin doses showed greater efficacy in improving oxidative stress.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Dyslipidemia is a key target in chronic kidney disease (CKD) treatment.
  • Lipid-lowering therapy aims to manage dyslipidemia in CKD patients.
  • The impact of hypolipidemic drugs on low molecular weight (LMW) thiols bound to LDL in CKD requires further investigation.

Purpose of the Study:

  • To evaluate the effect of different hypolipidemic drug regimens on LMW thiols and oxidative stress markers in CKD patients.
  • To compare the efficacy of simvastatin monotherapy versus ezetimibe/simvastatin combination therapy.

Main Methods:

  • Pilot study involving thirty CKD patients randomized into three groups.
  • Treatment regimens included simvastatin alone (40 mg/day) or combined ezetimibe/simvastatin (10/20 or 10/40 mg/day).
  • Evaluated LMW thiols (reduced and total forms), malondialdehyde, and allantoin/uric acid ratio.

Main Results:

  • LDL thiolation decreased in all treated groups.
  • Combined therapy with higher simvastatin dose (10/40 mg/day) demonstrated greater efficacy, achieving a 31% decrease in S-bound thiols after 1 year.
  • This group also showed a >40% reduction in apoB-Hcy, with a concomitant decrease in oxidative stress markers.

Conclusions:

  • Lipid-lowering therapy, particularly combined ezetimibe/simvastatin, effectively reduces LDL thiolation in CKD patients.
  • The observed improvement in oxidative stress suggests a potential mechanism for the beneficial effects of these therapies.
  • Reduced LDL-S-homocysteinylation may mitigate the antiangiogenic and proatherogenic effects on vascular endothelial cells.

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