COMPOSITIONAL AND FUNCTIONAL-CHANGES OF LOW-DENSITY-LIPOPROTEIN DURING HEMODIALYSIS IN PATIENTS WITH ESRD

Background. This study focused on the effects of hemodialysis on the a therogenic properties of low density lipoprotein (LDL) in patients wit h end-stage renal disease (ESRD). The impact of cholesterol ester tran sfer protein (CETP) activity and lipolysis on LDL composition, particu larly the changes during hemodialysis, was investigated. Methods. Bloo d was drawn from 15 normotriglyceridemic (NTG) and 15 hypertriglycerid emic patients [HTG; triglycerides (TG) <2.2 mmol/liter] before hemodia lysis, during (1.5 hr after the beginning of anticoagulation) and at t he end of treatment. In each sample, lipid values and CETP activity we re measured. LDL was prepared and characterized by its components and diameters (2 to 16% PAGGE). To investigate the functional properties o f LDL, fractions obtained from NTG and HTG patients were incubated wit h human skin fibroblasts and a cell line of murine macrophages (P388), and cholesterol ester formation rates were measured. Results. In comp arison to LDL from NTG patients at baseline, HTG-LDL were enriched in triglycerides (P < 0.02), depleted in cholesterol proportion (P < 0.01 ) and small in size (P < 0.001). These LDL induced the cholesterol est erification rates (50 mu g/mL LDL-protein) in a twofold greater unsatu ration in macrophages when compared to LDL from NTG patients (P < 0.04 ). The rates in fibroblasts were reduced by approximately half (P < 0. 05). During hemodialysis, LDL were decreased in size (P < 0.001) and d epleted in TG (P < 0.01), particularly in the hypertriglyceridemic sta te. Although CETP activity increased during hemodialysis (P < 0.001), the cholesterol content remained unchanged. When HTG-LDL obtained duri ng hemodialysis were incubated with cells, esterification rates partic ularly in macrophages were markedly accelerated in comparison to the u nmodified lipoprotein at baseline (P < 0.05). Conclusion. LDL from HTG patients with ESRD was TG-enriched, CH-depleted and smaller in size. As the intracellular esterification rates induced by LDL, were related to the cellular uptake, these LDL were a superior substrate for murin e macrophages with the tendency of intracellular accumulation, and an inferior substrate for fibroblasts suggesting a decreased uptake by th e specific receptor pathway. TG-depletion of LDL during hemodialysis, particularly in HTG patients due to a lipase-mediated TG-hydrolysis, i ncreased these effects in macrophages. We suggest that the alterations of LDL that occur during repeated hemodialysis bt vivo could contribu te to the high prevalence of premature atherosclerosis found in HTG pa tients with ESRD.