title: Effect of cholesterol lowering treatment on plasma markers of endothelial dysfunction in chronic kidney disease.
abstract: The elevated cardiovascular morbidity and mortality in chronic kidney disease (CKD) is linked with endothelial dysfunction secondary to the pro-inflammatory and pro-oxidative state typical of this pathology. In consideration of the well-known pleiotropic effect of statins, we investigated the effect of cholesterol lowering treatment on endothelial dysfunction markers (MED), asymmetric dimethylarginine (ADMA), vascular cell (VCAM) and intercellular (ICAM) adhesion molecule. Plasma MED concentrations, inflammation and oxidative stress indices [Kynurenine/Tryptophan (Kyn/Trp) ratio, malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio] were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40mg/day, ezetimibe/simvastatin 10/20mg/day, or ezetimibe/simvastatin 10/40mg/day). Treatment significantly reduced ADMA concentrations in all patients [0.694μmol/L (0.606-0.761) at baseline vs. 0.622μmol/L (0.563-0.681) after treatment, p<0.001]. ADMA reduction was paralleled by a significant decrease of MDA, All/AU ratio and Kyn/Trp ratio, but not VCAM and ICAM plasma concentrations. Cholesterol lowering treatment was associated with a significant reduction in plasma ADMA concentrations in CKD patients. This might be mediated by reduced oxidative stress and inflammation.
authors.affiliation: Department of Biomedical Sciences - University of Sassari, Sassari, Italy. Electronic address: azinellu@uniss.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Zinellu
authors.affiliation: Department of Biomedical Sciences - University of Sassari, Sassari, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sotgia
authors.affiliation: Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia.
authors.forename: Arduino A
authors.initials: AA
authors.lastname: Mangoni
authors.affiliation: Department of Biomedical Sciences - University of Sassari, Sassari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Sotgiu
authors.affiliation: Department of Biomedical Sciences - University of Sassari, Sassari, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ena
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences - University of Sassari, Sassari, Italy.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Satta
authors.affiliation: Department of Biomedical Sciences - University of Sassari, Sassari, Italy. Electronic address: carru@uniss.it.
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Carru
mesh_terms: D000481:Allantoin / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D002784:Cholesterol / Q000097:blood*; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism*; D000069438:Ezetimibe / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D019821:Simvastatin / Q000627:therapeutic use; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D014527:Uric Acid; D007737:Kynurenine; D000481:Allantoin; D008315:Malondialdehyde; C018524:N,N-dimethylarginine; D001120:Arginine; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe
keywords: Asymmetric dimethylarginine; Chronic kidney disease; Ezetimibe; Intercellular adhesion molecule; Oxidative stress; Simvastatin; Vascular cell adhesion molecule