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NDT Advance Access published online on July 17, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp342
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Low-density lipoprotein apheresis for haemodialysis patients with peripheral arterial disease reduces reactive oxygen species production via suppression of NADPH oxidase gene expression in leucocytes

Taiga Hara1, Hideyasu Kiyomoto1, Hirofumi Hitomi1, Kumiko Moriwaki1, Genei Ihara1, Kumiko Kaifu1, Yoshiko Fujita1, Chikako Higashiyama1, Akira Nishiyama2 and Masakazu Kohno1

1 Department of CardioRenal and Cerebrovascular Medicine 2 Department of Pharmacology, Faculty of medicine, Kagawa University, Kagawa, Japan

Correspondence and offprint requests to: Hideyasu Kiyomoto; E-mail: kiyo{at}kms.ac.jp



  Abstract

Background. Peripheral arterial disease (PAD) is a major complication of haemodialysis (HD), especially in patients with diabetes mellitus. Although previous reports have indicated that low-density lipoprotein apheresis (LDL-A) improves arteriosclerosis in PAD patients, the mechanism by which LDL-A affects PAD is still unclear. In this study, we tested the hypothesis that LDL-A attenuates reactive oxygen species (ROS) production in HD patients with PAD.

Methods. Twenty HD patients with PAD were investigated in this study. Clinical effects were evaluated by thermography and angiography. Oxidative stress in serum was evaluated by thiobarbituric acid reactive substances (TBARS) and expression of p22phox mRNA.

Results. Ischaemic symptoms due to PAD were gradually improved in 13 patients (65%) after LDL-A. One session of LDL-A removed ~75% of LDL from serum. Some patients exhibited dramatic improvement of severe symptoms of PAD such as skin ulcers after serial performance of LDL-A. The levels of LDL cholesterol, malondialdehyde-modified LDL, high-sensitivity C-reactive protein, vascular endothelial growth factor, international normalized ratio of pro-thrombin time and bradykinin were decreased after a single session of LDL-A, although there were no additional changes after 10 sessions of LDL-A. The levels of fibrinogen and p22phox mRNA were decreased by a single session of LDL-A, and these decreases continued over the entire period of treatment. TBARS was decreased after a course of LDL-A.

Conclusions. LDL-A improved ischaemic symptoms in HD patients with PAD by reducing ROS production in leucocytes. We conclude that LDL-A is an effective therapy for patients with HD complicated by PAD.

Keywords: NADPH oxidase; p22phox; thiobarbituric acid reactive substance (TBARS); oxidative stress; C-reactive protein (CRP)

Received for publication: 11.11.08
Accepted in revised form: 22. 6.09


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