Acute effect of simvastatin on inflammation and oxidative stress in chronic kidney disease.
BACKGROUND
Inflammation and oxidative stress (OS) are risk factors for cardiovascular disease in chronic kidney disease (CKD). This study assessed the acute effect of simvastatin on inflammatory and OS markers in stage 3 and 4 CKD patients.


METHODS
Randomized, placebo-controlled, double-blind, cross-over study comprising 66 patients who were randomized to simvastatin (20 mg/day) or placebo for two 8-week periods. Glomerular filtration rate (GFR), lipid profile, C-reactive protein (CRP), fibrinogen, carbonyls and total radical-trapping antioxidant potential (TRAP) were measured. Interactions between potential confounding factors, such as diabetes mellitus, malnutrition, drug use, hypercholesterolemia and treatment response were assessed through the course of inflammatory and OS levels.


RESULTS
Thirty-three patients were randomized to simvastatin/placebo (S-P), and 33 to placebo/simvastatin (P-S). Simvastatin significantly reduced total and LDL cholesterol (pretreatment vs. posttreatment: p=0.0001 and p=0.0001, respectively) in both periods. No differences were seen in CRP, fibrinogen, carbonyls and TRAP levels between S-P and P-S groups at the end of the 2 study periods. GFR was similar in both groups and negatively correlated to fibrinogen (r=-0.25, p=0.04) and TRAP (r=-0.27, p=0.03). No interactions were found between confounding factors and response to simvastatin. There was no interference of either a period effect or any carryover effect on study results.


CONCLUSIONS
The use of simvastatin in CKD patients acutely did not reduce serum inflammation or OS markers. Possibly higher doses and/or longer treatment course of statin are required to produce drug pleiotropic effects in nondialysis CKD patients.
Dummer
Claus D
CD
Graduate Program in Medical Sciences, Nephrology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul - Brazil.
Thome'
Fernando S
FS
Zingano
Bianca
B
Lindoso
Alberto
A
Veronese
Francisco V
FV
D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D009752:Nutritional Status / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D012189:Retrospective Studies; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D005340:Fibrinogen; D002097:C-Reactive Protein; D019821:Simvastatin; D003404:Creatinine