Treatment of dyslipidemia in chronic kidney disease: Effectiveness and safety of statins.

Several cardiovascular (CV) risk factors may explain the high rate of CV death among patients with chronic kidney disease (CKD). Among them both traditional and uremia-related risk factors are implicated and, moreover, the presence of kidney disease represents "per se" a multiplier of CV risk. Plasma lipid and lipoprotein profiles are changed in quantitative, but above all in qualitative, structural, and functional ways, and lipoprotein metabolism is influenced by the progressive loss of renal function. Statin therapy significantly reduces cholesterol synthesis and both CV morbidity and mortality either directly, by reducing the lipid profile, or via pleiotropic effects; it is supposed to be able to reduce both the progression of CKD and also proteinuria. These observations derive from a post-hoc analysis of large trials conducted in the general population, but not in CKD patients. However, the recently published SHARP trial, including over 9200 patients, either on dialysis or pre-dialysis, showed that simvastatin plus ezetimibe, compared with placebo, was associated with a significant low-density lipoprotein cholesterol reduction and a 17% reduction in major atherosclerotic events. However, no benefit was observed in overall survival nor in preserving renal function in patients treated. These recent data reinforce the conviction among nephrologists to consider their patients at high CV risk and that lipid lowering drugs such as statins may represent an important tool in reducing atheromatous coronary disease which, however, represents only a third of CV deaths in patients with CKD. Therefore, statins have no protective effect among the remaining two-thirds of patients who suffer from sudden cardiac death due to arrhythmia or heart failure, prevalent among CKD patients. The safety of statins is demonstrated in CKD by several trials and recently confirmed by the largest SHARP trial, in terms of no increase in cancer incidence, muscle pain, creatine kinase levels, severe rhabdomyolysis, hepatitis, gallstones and pancreatitis; thus confirming the handiness of statins in CKD patients. Here we will review the latest data available concerning the effectiveness and safety of statin therapy in CKD patients.