Atherogenic lipoproteins in end-stage renal disease

Cardiovascular mortality is substantially higher in patients with end-stage renal disease (ESRD). Lipoprotein abnormality in ESRD is one of the possible risk factors for advanced atherosclerosis. Uremic dyslipidemia is characterized by increased plasma triglycerides due to elevated very low density lipoprotein (VLDL) and decreased high-density lipoprotein (HDL). Plasma total or low-density lipoprotein (LDL) cholesterol is rarely elevated in hemodialysis patients. The "LDL" by standard assay methods consists of intermediate-density lipoprotein (IDL) and LDL devoid of IDL. Although "LDL" is not increased, IDL is markedly elevated in uremic plasma. We previously showed that aortic stiffness of hemodialysis patients was associated positively with VLDL, IDL, and LDL devoid of IDL and that IDL is the best lipoprotein predictor of aortic stiffness. The IDL level is correlated positively with plasma total cholesterol, triglyceride, and "LDL" levels. Importantly, increased IDL is found in ESRD patients with "normal" "LDL"cholesterol levels, indicating that the target "LDL" level should be lower than that for the general population. More than 40% of hemodialysis patients exceeded the upper limit (15 mg/dL, 95th percentile level) of IDL cholesterol in healthy subjects. Based on a linear relationship between IDL and "LDL," the normal range of IDL cholesterol (<15 mg/dL) corresponds to "LDL" cholesterol by the Friedewald equation below 100 mg/dL in hemodialysis patients. Statins effectively and safely reduce "LDL," including IDL in patients treated with hemodialysis or peritoneal dialysis. The effect of lipid-lowering therapy on cardiovascular mortality in ESRD, however, awaits the results of ongoing prospective trials.