Abnormalities in lipoprotein metabolism in hemodialysis patients.
BACKGROUND
Patients on chronic hemodialysis treatment are at elevated atherogenic risk, and dyslipidemia appears to be one of the major risk factors. However, most of these patients exhibit elevated serum triglycerides, whereas serum cholesterol and low-density lipoprotein (LDL) cholesterol levels are in the normal range. This study was therefore designed to examine the influence of hypertriglyceridemia under the condition of hemodialysis and diabetes mellitus on LDL metabolism.


METHODS
LDL was isolated from healthy controls, hypertriglyceridemic diabetic patients, and nondiabetic hemodialysis patients (N = 30, 10 in each group), which were separated into six subfractions by density gradient ultracentrifugation and were characterized concerning lipid/protein composition, degree of glycation, and oxidation. Uptake of 125I-labeled LDL was examined via LDL receptors of HepG2 cells and scavenger receptors of mouse peritoneal macrophages.


RESULTS
In hemodialysis patients, serum triglycerides were significantly elevated, whereas cholesterol levels were within the normal range. Triglyceride enrichment occurred in the very low-density lipoprotein (VLDL) class and LDL class, and an accumulation of a highly atherogenic small dense LDL subfraction could be detected predominantly in patients with non-insulin-dependent diabetes mellitus. LDL of hemodialysis patients also contained elevated levels of lipid peroxidation products, which were even higher in diabetic patients. Alterations in composition, size, and configuration of LDL from diabetic and nondiabetic patients on hemodialysis impaired LDL receptor-mediated degradation and enhanced the uptake of these modified LDL particles via nonsaturable scavenger receptors.


CONCLUSIONS
Diminished LDL receptor-mediated uptake of modified, triglyceride-rich, small dense LDL most likely leads to accumulation of these lipoproteins in vivo, favoring the development of atherosclerotic lesions. Future clinical studies must demonstrate whether patients will benefit from reducing these atherogenic particles by lipid-lowering intervention.
Department of Medicine, University of Freiburg, Germany. koeniger@mm41.ukl.uni-freiburg.de
M
M
Königer
T
T
Quaschning
C
C
Wanner
P
P
Schollmeyer
A
A
Krämer-Guth
D001055:Apolipoproteins B / Q000378:metabolism; D001667:Binding, Competitive; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D006031:Glycosylation; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications; D007457:Iodine Radioisotopes; D015227:Lipid Peroxidation; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D006435:Renal Dialysis; D014280:Triglycerides / Q000097:blood; D014407:Tumor Cells, Cultured
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D007457:Iodine Radioisotopes; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides