Possible nephrotoxic effects of high dose statin therapy; current knowledge

Introduction The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors (i.e., statins) are recommended as a first-line of cholesterol-lowering medication for lipid control. Statins reduce low-density lipoprotein cholesterol (LDL-c), a chief contributor to atherosclerotic cardiovascular disease, which helps prevent cardiovascular disease. Recent studies demonstrate that high-dose statins augment LDL-c reduction and lead to improving cardiovascular outcomes compared to lowor moderatedose statin therapy in atherosclerotic cardiovascular disease patients (1). The benefits of high-dose statin therapy on cardiovascular risks have increased prescribing of high-dose statins. Despite beneficial effects with statin therapy, treatment with these agent is also associated with adverse events. These adverse effects range from nonthreatening asymptomatic presentations to severe organ dysfunction, especially of the kidneys and liver. Severe adverse effects associated with statin treatment include muscle damage, renal failure, liver dysfunction and polyneuropathy. Specific side effects of renal origin include rhabdomyolysis, proteinuria and acute kidney injury (AKI). Acute kidney injury Several clinical studies propose that high-dose statin treatment will increase the risk of AKI. However, cardiovascular surgery patients may respond differently to the type and dose of statin therapy. For instance, highdose statins are associated with a high risk of AKI in patients of the general population. In contrast, equivalent doses of those statins in cardiovascular surgery patients demonstrated renoprotective effects (2). Numerous studies suggest that high-dose statins will significantly increase the risk of contrast-induced AKI. A previous study has demonstrated a relationship between the high dose of atorvastatin and renal injury if administered alone or in combination with high doses of garlic; while a low-dose of atorvastatin in combination with high doses of garlic has negligible nephrotoxic effects (3). Statins should be administered cautiously in coronary artery disease patients undergoing coronary angiography (3,4). Hospitalization due to AKI was 34% higher in the cohort that received high-dose statin therapy compared to the cohort that administered low-dose statin therapy (2). High doses of atorvastatin have nephrotoxic effects, while lower doses have beneficial effects on renal function and structure (2) suggesting that, high doses of statins may be Ep id em io lo gy a nd P re ve nt io n