Neutral-Lipid Transfers and Cholesteryl Ester Transfer Protein in Hemodialyzed Patients

Background: Plasma levels of small, dense low-density lipoprotein (LDL) were reported to increase in chronic kidney disease (CKD) patients on hemodialysis (HD), but most of these patients were hypertriglyceridemic. Plasma levels of small, dense LDL are known to increase in hypertriglyceridemic subjects. Therefore, to investigate the direct effect of CKD on the distribution of LDL subfractions, we investigated the distribution of LDL subfractions in normotriglyceridemic CKD patients on HD. Methods: The levels of plasma lipoprotein subfractions and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), which markedly influence the distributions of plasma LDL and high-density lipoprotein (HDL) subfractions, were compared between 40 HD patients and 40 normolipidemic controls. Plasma lipoproteins were subfractionated into seven subfractions by ultracentrifugation. Results: Plasma levels of cholesterol (C) in remnant-like particle, which is equivalent to the triglyceride (TG)-rich lipoprotein remnant, were twice as high in HD patients as those in controls with matched TG levels. Plasma levels of C and TG in VLDL and IDL (intermediate density lipoprotein) were slightly higher in HD patients than in controls. The C/TG ratio of VLDL was significantly higher in HD patients than in controls. In comparison with the corresponding values in controls, the C and TG levels in low-density LDL and HDL₂ in HD patients were high, whereas those in medium-density LDL, high-density LDL, and HDL₃ were low. Plasma LCAT activity and CETP mass were lower in HD patients than in controls. Conclusion: Distribution of LDL and HDL skewed toward less dense fractions in normotriglyceridemic CKD patients on HD. A decrease in reverse C transport likely played an important role in these changes in the patients.

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“…We obtained similar results. However, the results for CETP were not the same [30,31,32]. CETP mass was low in HD patients in this study.…”

Section: Discussioncontrasting

confidence: 58%

Skew of Plasma Low- and High-Density Lipoprotein Distributions to Less Dense Subfractions in Normotriglyceridemic Chronic Kidney Disease Patients on Maintenance Hemodialysis Treatment

Homma

Shiina

et al. 2013

Nephron Clin Pract

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“…In Japan, HD patients were found to have low levels and activity of hepatic lipase (4,5). In addition, CETP was significantly lower in HD patients than in control subjects (Table 1) (10). Thus, these abnormalities in HD patients delay the transport of cellular cholesterol to the liver.…”

Section: Discussionmentioning

confidence: 99%

“…Rather, their lipoprotein profiles are characterized by reduced HDL-cholesterol (HDL-C) and elevated triglyceride (TG)-rich lipoprotein concentrations (3)(4)(5)(6). In addition, the enzymes and transfer proteins involved in lipoprotein metabolism tend to exhibit lowered activity in HD patients (4,5,(7)(8)(9)(10). These abnormalities may contribute significantly to the high frequency of CVD occurrence in HD patients.…”

mentioning

confidence: 99%

LCAT-Dependent Conversion of Preβ1-HDL into α-Migrating HDL is Severely Delayed in Hemodialysis Patients

Miida¹,

Miyazaki²,

Hanyu

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Pre␤1-HDL is a minor HDL subfraction that acts as an efficient initial acceptor of cell-derived free cholesterol. During 37°C incubation, plasma pre␤1-HDL decreases over time due to its conversion to ␣-migrating HDL by lecithin: cholesterol acyltransferase (LCAT). This conversion may be delayed in hemodialysis patients who have decreased LCAT activity. To clarify whether LCAT-dependent conversion of pre␤1-HDL to ␣-migrating HDL is delayed in hemodialysis patients, pre␤1-HDL concentrations were determined in 45 hemodialysis patients and 45 gender-matched control subjects before and after 37°C incubation with and without the LCAT inhibitor. It was found that the baseline pre␤1-HDL concentration in hemodialysis patients was more than twice that in the controls (44.9 Ϯ 21.4 versus 19.8 Ϯ 6.7 mg/L apoAI; P Ͻ 0.001). After 2-h incubation, the LCAT-dependent decrease in pre␤1-HDL in hemodialysis patients was about one-third of that in the controls (30 Ϯ 27 versus 97 Ϯ 17% of baseline; P Ͻ 0.01). The LCAT-dependent rate of decrease in pre␤1-HDL levels (DR pre␤1 ) was the same for samples from hemodialysis patients exhibiting normal (Ն1.03 mmol/L) and low HDLcholesterol levels (32 Ϯ 32 versus 28 Ϯ 23% of baseline; NS). DR pre␤1 was positively correlated with LCAT activity (r ϭ 0.617; P Ͻ 0.001). In conclusion, the LCAT-dependent conversion of pre␤1-HDL to ␣-migrating HDL is severely delayed in hemodialysis patients. The impaired catabolism of pre␤1-HDL may accelerate atherosclerosis in hemodialysis patients.

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“…In particular, lipoprotein lipase (LPL) and hepatic lipase activities are significantly decreased. 8 As observed earlier in patients with hypertriglyceridemia 4 increased plasma TG level per se might constitute a major contributor to elevated cholesteryl ester transfer protein (CETP) activity in HD patients, and both HD per se and chronic renal failure would contribute in a complementary manner to these abnormalities. 4 During HD, heparin that is used as an anticoagulant to prevent clotting in the extra corporeal devices releases LPL from its binding sites at the vascular endothelium.…”

mentioning

confidence: 84%

“…In contrast, total and low-density lipoprotein (LDL) cholesterol levels usually remain in the normal range. [4][5][6][7] Although the etiology of the HD-associated dyslipidemia has not been fully established, alterations of several enzymes involved in lipoprotein metabolism are commonly observed. In particular, lipoprotein lipase (LPL) and hepatic lipase activities are significantly decreased.…”

mentioning

confidence: 99%

Hemodialysis reduces plasma apolipoprotein C-I concentration making VLDL a better substrate for lipoprotein lipase

Dautin

Soltani²,

Ducloux

et al. 2007

Kidney International

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Apolipoprotein Cs (apoC-1, apoC-II, and apoC-III) are lipoprotein components that have regulatory effects on enzymes involved in lipoprotein metabolism. Owing to their low molecular weights, apoCs can adsorb onto and/or pass through dialysis membranes. Our study determines the consequence of hemodialysis (HD) on plasma concentrations of apoCs and on the activities of enzymes modulated by apoCs. Plasma samples were collected from 28 patients with chronic renal failure before and after HD. Plasma apoC-II levels were unchanged, whereas apoC-III levels were slightly decreased in post-dialysis plasmas. The apoC-I content was markedly reduced during HD. This was due to a significant decrease in the apoC-I content of very low-density lipoprotein (VLDL), whereas the apoC-I content of high-density lipoprotein (HDL) was unchanged. Although HDL bound apoC-I is thought to inhibit cholesterol ester transfer protein, no change in the ability of pre- and post-dialysis VLDL to interact with the transfer protein were observed. Complementary experiments confirmed that VLDL-bound apoC-I has no transfer protein inhibitory potential. In contrast, an increase in the ability of post-dialysis apoC-I-poor VLDL to act as substrate for lipoprotein lipase (LPL) was found compared to pre-dialysis VLDL. Our study shows that apoC-I losses during HD might be beneficial by improving the ability of VLDL to be a substrate for LPL thus improving plasma triglyceride metabolism.

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Neutral-Lipid Transfers and Cholesteryl Ester Transfer Protein in Hemodialyzed Patients

Cited by 5 publications

References 23 publications

Skew of Plasma Low- and High-Density Lipoprotein Distributions to Less Dense Subfractions in Normotriglyceridemic Chronic Kidney Disease Patients on Maintenance Hemodialysis Treatment

Skew of Plasma Low- and High-Density Lipoprotein Distributions to Less Dense Subfractions in Normotriglyceridemic Chronic Kidney Disease Patients on Maintenance Hemodialysis Treatment

LCAT-Dependent Conversion of Preβ1-HDL into α-Migrating HDL is Severely Delayed in Hemodialysis Patients

Hemodialysis reduces plasma apolipoprotein C-I concentration making VLDL a better substrate for lipoprotein lipase

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