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Defective high-density lipoprotein composition in patients on chronic hemodialysis. A possible mechanism for
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Patients on chronic hemodialysis exhibit significantly reduced high-density lipoprotein cholesterol and abnormal lipoprotein composition, potentially increasing atherosclerosis risk. Altered apoprotein levels may also contribute to elevated triglyceride levels in these patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Biochemistry
Background:
- Chronic kidney disease patients on hemodialysis often present with dyslipidemia.
- Altered lipid profiles, particularly reduced high-density lipoprotein (HDL) cholesterol, are common in this population.
- The specific apoprotein structure abnormalities in HDL and very-low-density lipoprotein (VLDL) in hemodialysis patients require further elucidation.
Purpose of the Study:
- To determine serum HDL cholesterol content in patients undergoing chronic hemodialysis.
- To analyze the apoprotein structure of various lipoprotein fractions in these patients.
- To investigate the relationship between lipid abnormalities, apoprotein composition, and atherosclerosis risk in hemodialysis patients.
Main Methods:
- Serum samples were collected from 21 patients on chronic hemodialysis and 11 healthy controls.
- High-density lipoprotein cholesterol levels were quantified.
- Apoprotein structure of lipoprotein fractions (VLDL, HDL subfractions) was analyzed using electrophoresis.
Main Results:
- Hemodialysis patients showed significantly reduced HDL cholesterol compared to controls (26 ± 13 vs. 52 ± 9 mg/100 ml).
- In patients with Type IV hyperlipoproteinemia, HDL and its subfractions (1, 2, 3) had reduced protein and cholesterol content.
- Apoprotein electrophoresis revealed increased arginine-rich peptide and decreased apoprotein C-II in VLDL and HDL fractions.
Conclusions:
- Patients on chronic hemodialysis have significantly lower HDL cholesterol levels and abnormal HDL composition.
- Abnormalities in HDL apoprotein structure, including reduced apoprotein C-II, may contribute to atherosclerosis in these patients.
- Defective lipoprotein lipase activation due to reduced VLDL apoprotein may explain elevated triglyceride levels.
Abstract:
We determined serum high-density lipoprotein cholesterol content and analyzed the approtein 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 less than 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 less than 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 Cll 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.