Background/Aim: In patients with end-stage renal disease (ESRD), cardiovascular complications are the main cause of death. Increased oxidative stress is one of the risk factors for enhanced atherosclerosis in this population. Literature data vary partially dependent on differences in methodology. The present study compares three different methods: plasma lipid peroxides, the newly developed measurement of circulating oxidized LDL (Ox-LDL) particles and the frequently used copper-induced LDL oxidation lag time. Methods: We assessed plasma lipid peroxides, circulating Ox-LDL and in vitro copper-induced LDL oxidation lag time in 47 non-diabetic patients with ESRD, at the start of renal replacement therapy, and compared these with 41 age- and sex-matched controls. Results: In ESRD, total cholesterol (4.6 ± 1.1 vs. 5.6 ± 0.9 mmol/l; p < 0.001), LDL cholesterol (2.8 ± 0.8 vs. 3.5 ± 0.7 mmol/l; p < 0.001) and HDL cholesterol (1.0 ± 0.3 vs. 1.4 ± 0.4 mmol/l; p < 0.001) were lower compared to controls. Plasma lipid peroxides were higher (1.1 ± 0.5 vs. 0.8 ± 0.5 µmol/l; p = 0.003) in ESRD. No differences were observed in plasma Ox-LDL (63.1 ± 62.0 vs. 55.3 ± 48.0 mg/l). However, due to the lower plasma LDL cholesterol in ESRD, LDL oxidation level was increased in ESRD (7.1 ± 0.1 vs. 4.2 ± 0.3%; p = 0.03). LDL lag time was slightly longer (89 ± 11 vs. 84 ± 11 min; p = 0.04) in ESRD. There were no significant differences regarding the amount and rate of dienes produced. Conclusions: Elevated levels of lipid peroxides and higher LDL oxidation levels support the theory that ESRD is associated with increased oxidative stress, which may explain the accelerated atherosclerosis. The measured amount of oxidative stress is not reflected by in vitro oxidizability of LDL.

1.
Levey AS, Eknoyan G: Cardiovascular disease in chronic renal disease. Nephrol Dial Transplant 1999;14:828–833.
2.
Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM: The elephant in uremia: Oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int 2002;62:1524–1538.
3.
Takenaka T, Takahashi K, Kobayashi T, Oshima E, Iwasaki S, Suzuki H: Oxidized low density lipoprotein as a marker of atherosclerosis in hemodialysis patients. Clin Nephrol 2002;58:33–37.
4.
Galle J: Oxidative stress in chronic renal failure. Nephrol Dial Transplant 2001;16:2135–2137.
5.
Galli F, Canestrari F, Bellomo G: Pathophysiology of the oxidative stress and its implication in uremia and dialysis. Contrib Nephrol. Basel, Karger, 1999, vol 127, pp 1–31.
6.
Annuk M, Fellstrom B, Akerblom O, Zilmer K, Vihalemm T, Zilmer M: Oxidative stress markers in pre-uremic patients. Clin Nephrol 2001;56:308–314.
7.
Handelman GJ, Walter MF, Adhikarla R, Gross J, Dallal GE, Levin NW, Blumberg JB: Elevated plasma F2-isoprostanes in patients on long-term hemodialysis. Kidney Int 2001;59:1960–1966.
8.
Loughrey CM, Young IS, McEneny J, McDowell IF, McMaster C, McNamee PT, Trimble ER: Oxidation of low-density lipoprotein in patients on regular haemodialysis. Atherosclerosis 1994;110:185–193.
9.
Roob JM, Rabold T, Hayn M, Khoschsorur G, Resch U, Holzer H, Winklhofer-Roob BM: Ex vivo low-density lipoprotein oxidizability and in vivo lipid peroxidation in patients on CAPD. Kidney Int Suppl 2001;78:128–136.
10.
Schulz T, Schiffl H, Scheithe R, Hrboticky N, Lorenz R: Preserved antioxidative defense of lipoproteins in renal failure and during hemodialysis. Am J Kidney Dis 1995;25:564–571.
11.
Westhuyzen J, Saltissi D, Healy H: Oxidation of low density lipoprotein in hemodialysis patients: Effect of dialysis and comparison with matched controls. Atherosclerosis 1997;129:199–205.
12.
Jackson MJ: An overview of methods for assessment of free radical activity in biology. Proc Nutr Soc 1999;58:1001–1006.
13.
Esterbauer H, Striegl G, Puhl H, Rotheneder M: Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun 1989;6:67–75.
14.
Holvoet P, Donck J, Landeloos M, Brouwers E, Luijtens K, Arnout J, Lesaffre E, Vanrenterghem Y, Collen D: Correlation between oxidized low density lipoproteins and von Willebrand factor in chronic renal failure. Thromb Haemost 1996;76:663–669.
15.
Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, Van de WF: Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2001;21:844–848.
16.
Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502.
17.
Princen HM, van Poppel G, Vogelezang C, Buytenhek R, Kok FJ: Supplementation with vitamin E but not β-carotene in vivo protects low-density lipoprotein from lipid peroxidation in vitro. Effect of cigarette smoking. Arterioscler Thromb 1992;12:554–562.
18.
Kleinveld HA, Hak-Lemmers HL, Stalenhoef AF, Demacker PN: Improved measurement of low-density lipoprotein susceptibility to copper-induced oxidation: Application of a short procedure for isolating low-density lipoprotein. Clin Chem 1992;38:2066–2072.
19.
Van Tits L, De Graaf J, Hak-Lemmers H, Bredie S, Demacker P, Holvoet P, Stalenhoef A: Increased levels of low-density lipoprotein oxidation in patients with familial hypercholesterolemia and in end-stage renal disease patients on hemodialysis. Lab Invest 2003;83:13–21.
20.
Annuk M, Zilmer M, Lind L, Linde T, Fellstrom B: Oxidative stress and endothelial function in chronic renal failure. J Am Soc Nephrol 2001;12:2747–2752.
21.
Selvaraj N, Bobby Z, Das AK, Ramesh R, Koner BC: An evaluation of level of oxidative stress and protein glycation in nondiabetic undialyzed chronic renal failure patients. Clin Chim Acta 2002;324:45–50.
22.
Massy ZA, Nguyen-Khoa T: Oxidative stress and chronic renal failure: Markers and management. J Nephrol 2002;15:336–341.
23.
Kleinveld HA, Naber AH, Stalenhoef AF, Demacker PN: Oxidation resistance, oxidation rate, and extent of oxidation of human low-density lipoprotein depend on the ratio of oleic acid content to linoleic acid content: Studies in vitamin E deficient subjects. Free Radic Biol Med 1993;15:273–280.
24.
Reaven P, Parthasarathy S, Grasse BJ, Miller E, Steinberg D, Witztum JL: Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects. J Clin Invest 1993;91:668–676.
25.
Morena M, Cristol JP, Dantoine T, Carbonneau MA, Descomps B, Canaud B: Protective effects of high-density lipoprotein against oxidative stress are impaired in haemodialysis patients. Nephrol Dial Transplant 2000;15:389–395.
26.
Williams MJ, Sutherland WH, McCormick MP, De Jong SA, McDonald JR, Walker RJ: Vitamin C improves endothelial dysfunction in renal allograft recipients. Nephrol Dial Transplant 2001;16:1251–1255.
27.
Van Den Akker JM, Bredie SJH, Diepeveen SHA, Van Tits LJH, Stalenhoef AFH, Van Leusen R: Atorvastatin and simvastatin in patients on hemodialysis: Effects on lipoproteins, C-reactive protein and in vivo oxidized LDL. J Nephrol 2003;16:238–244.
28.
Vasankari T, Ahotupa M, Toikka J, Mikkola J, Irjala K, Pasanen P, Neuvonen K, Raitakari O, Viikari J: Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: Lower levels of oxidized LDL with statin therapy. Atherosclerosis 2001;155:403–412.
29.
Ghiadoni L, Magagna A, Versari D, Kardasz I, Huang Y, Taddei S, Salvetti A: Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension 2003;41:1281–1286.
30.
Landmesser U, Drexler H: Oxidative stress, the renin-angiotensin system, and atherosclerosis. Eur Heart J Suppl 2003;5(suppl A):3–7.
31.
Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M, Green MS: Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): Randomised placebo-controlled trial. Lancet 2000;356:1213–1218.
32.
Tepel M, van der GM, Statz M, Jankowski J, Zidek W: The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: A randomized, controlled trial. Circulation 2003;107:992–995.
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