Defective High-Density Lipoprotein Composition in Patients on Chronic Hemodialysis: A Possible Mechanism for Accelerated Atherosclerosis

We determined serum high-density lipoprotein cholesterol content and analyzed the apoprotein structure of the various lipoprotein fractions in 21 patients on chronic hemodialysis. High-density lipoprotein cholesterol was significantly reduced in all patients as compared with 11 normal persons (mean ±1 standard deviation: 26±13 vs. 52±9 mg per 100 ml; P<0.001) whether or not triglyceride levels were raised. In seven of those with Type IV hyperlipoproteinemia, protein content of high-density lipoprotein and its subfractions 1, 2 and 3 were also reduced (P<0.001) in parallel with reductions in cholesterol in these fractions. Apoprotein electrophoresis showed an increase in “arginine-rich” peptide in very-low-density lipoprotein and high-density lipoprotein fraction 1, and a reduction in apoprotein CII in very-low-density and high-density lipoprotein. In addition to their reduced high-density lipoprotein cholesterol levels, a major factor in the atherosclerosis of these patients may be their abnormal high-density lipoprotein composition. Their raised triglyceride levels could be due to defective lipoprotein lipase activation by the reduced very-low-density lipoprotein apoprotein CII. (N Engl J Med 299:1326–1329, 1978) ACCELERATED atherosclerosis is a frequent complication in patients on chronic hemodialysis, and the major cause of death among these patients is atherosclerotic cardiovascular disease.¹ Considerable attention has been paid to the factors involved in this process, with a view both to reducing the morbidity and mortality of chronic uremia and to throwing light on the cause of the atherosclerotic process itself. One possible factor is the hyperlipidemia that frequently occurs in chronic renal failure. Type IV hyperlipoproteinemia is the most common type,² consisting of a raised triglyceride concentration in whole plasma and in the very-low-density lipoprotein fraction of plasma; cholesterol.