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.