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Among patients with preexisting coronary heart disease, large-scale randomized trials have demonstrated that lowering low-density lipoprotein (LDL)-cholesterol concentration by about 1 mmol/L for 4-5 years reduces the risk of coronary events and strokes by about 25%. Patients with established chronic kidney disease (CKD) are at high risk of vascular disease, so the benefits of cholesterol-lowering therapy might be expected to be substantial in this population. Patients with CKD have generally been excluded from previous trials, however, and there is currently no reliable randomized evidence that lowering LDL-cholesterol would be beneficial among them. There are several reasons why the demonstrated benefits of lowering blood cholesterol in other populations might not translate to patients with CKD. First, observational studies among dialysis patients have reported a negative association between blood total cholesterol and mortality. Second, only about one quarter of cardiac mortality in such patients appears to be attributable to acute myocardial infarction, and potentially avoidable with cholesterol lowering, while the other common causes (e.g., cardiac arrest, arrhythmia, and heart failure) may not be as dependent on cholesterol levels. Finally, the long-term safety of cholesterol reduction among patients with CKD remains unclear. Hence, there is an important need for reliable direct evidence on whether lowering cholesterol prevents a worthwhile proportion of vascular events, without unacceptable toxicity, among patients with CKD. The Study of Heart and Renal Protection (SHARP) aims to assess the effects of cholesterol-lowering therapy with a combination of simvastatin and the cholesterol-absorption inhibitor ezetimide among around 9000 patients with CKD.

Original publication




Journal article


Kidney int suppl

Publication Date



S207 - S210


Cholesterol, LDL, Coronary Disease, Humans, Hypolipidemic Agents, Kidney Failure, Chronic, Randomized Controlled Trials as Topic, Risk Factors, Stroke