Journal Article

Protective effects of high-density lipoprotein against oxidative stress are impaired in haemodialysis patients

Marion Morena, Jean-Paul Cristol, Thierry Dantoine, Marie-Annette Carbonneau, Bernard Descomps and Bernard Canaud

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 15, issue 3, pages 389-395
Published in print March 2000 | ISSN: 0931-0509
Published online March 2000 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/15.3.389
Protective effects of high-density lipoprotein against oxidative stress are impaired in haemodialysis patients

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Introduction. Cardiovascular diseases represent the major cause of mortality in haemodialysis (HD) patients. Oxidized low-density lipoprotein (Ox-LDL) is a major cardiovascular risk factor, implicated in atherosclerotic plaque formation. It has been suggested that high-density lipoprotein (HD) has the capacity to reduce the oxidative modifications of LDL. The aim of this study is to analyse the protective effects of HDL in HD patients.

Methods.In vitro copper-induced LDL oxidation was evaluated in 12 patients with chronic renal failure (mean age 61.0±12.8 years) and compared to 25 healthy subjects (mean age 57.3±19.2 years). LDL were incubated in oxygen-saturated PBS, LDL oxidation was initiated by Cu (II) in the presence and absence of HDL and assessed by measuring the absorbance (abs) increase at 234 nm due to conjugated diene formation. Duration of lag time, maximum velocity (Vmax.) of lipid peroxidation, oxidation slope and half-time of maximum diene formation (T ½) were obtained by kinetic modelling analysis.

Results. HDL (1.06±0.31 vs 1.23±0.39 mmol/l) and Apo AI (1.17±0.39 vs 1.49±0.20 g/l) levels were decreased in HD patients. In the absence of HDL, LDL obtained from HD patients showed an enhanced susceptibility to oxidation in vitro as demonstrated by the significant decrease in lag time (54.5±22.2 vs 79.4±37.8 min) and a significant increase in Vmax. (0.026±0.006 vs 0.017±0.005 abs/min). In all cases, HDL (from 0.1 to 2 μM) prevented LDL oxidation in vitro; however, this effect was significantly reduced in HD patients: increase in lag time 54.2% vs 150.4% in HD vs controls; increase in T ½ 52.2% vs 124.6% in HD vs controls; decrease in Vmax. 13.5% vs 38.5% in HD vs controls.

Conclusions. These results suggest that qualitative abnormalities such as an impairment of HDL-associated enzymes are associated with a decrease of HDL levels during HD. Hence, in addition to the known impairment of reverse cholesterol transport, the reduction of HDL protective capacity against oxidative stress could be involved in the development of HD-induced atherosclerosis.

Keywords: high-density lipoprotein; lipid peroxidation; low-density lipoprotein

Journal Article.  4208 words.  Illustrated.

Subjects: Nephrology

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