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Eicosapentanoic Acid Reduces Plasma Levels of Remnant Lipoproteins and Prevents in Vivo Peroxidation of LDL in Dialysis Patients

Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.

Correspondence to Dr. Minoru Ando, Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. Phone: +81 3 3353 8111, extension, 36412; Fax: +81 3 5269 7368.

Abstract. Causative factors of uremia-associated atherosclerosis are complex. However, it is likely that atherogenic lipoproteins accumulated in plasma are involved. Remnant lipoproteins are atherogenic and are frequently observed in uremic plasma. LDL from uremic patients has been shown to be susceptible to in vitro peroxidation, suggesting that oxidized LDL (ox-LDL) could be excessively generated in those patients. No effective treatments to prevent accumulation of both atherogenic lipoproteins in dialysis patients have been published. Eicosapentanoic acid (EPA) may change synthesis and/or catabolism of remnant lipoproteins and increase stability of LDL to peroxidation by altering the fatty acid composition of lipoproteins. A prospective comparative study was conducted to assess the efficacy of EPA on metabolism of remnant lipoproteins and ox-LDL in dialysis patients using two new methods: an immunoaffinity gel separation for quantifying plasma remnant lipoproteins and an enzyme-linked immunosorbent assay for measuring plasma ox-LDL levels, a marker for in vivo LDL peroxidation. Twenty-two hemodialysis and 16 continuous ambulatory peritoneal dialysis patients with relatively high plasma levels of remnant lipoproteins and ox-LDL were randomized to either EPA or placebo. Highly purified EPA, in an ethyl-ester form (ethyl all-cis-5,8,11,14,17-icosapentanoate) with a purity greater than 91%, was administered at a dose of 1800 mg daily. Overall, 3 mo of treatment with EPA significantly reduced the levels of both remnant lipoproteins (52% reduction) and ox-LDL (38% reduction). Additionally, gel filtration chromatography of lipoproteins showed that EPA treatment concomitantly normalized other potential abnormalities in lipoproteins. Treatment compliance was good and no critical adverse effects were observed. In conclusion, EPA administration proved to be effective and safe treatment to decrease plasma remnant lipoproteins and prevent in vivo peroxidation of LDL in dialysis patients.

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