title: 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.
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 approximately 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.
authors.affiliation: Department of CardioRenal and Cerebrovascular Medicine, Faculty of medicine, Kagawa University, Kagawa, Japan.
authors.forename: Taiga
authors.initials: T
authors.lastname: Hara
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kiyomoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Kumiko
authors.initials: K
authors.lastname: Moriwaki
authors.forename: Genei
authors.initials: G
authors.lastname: Ihara
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kaifu
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Chikako
authors.initials: C
authors.lastname: Higashiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001781:Blood Component Removal; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008077:Lipoproteins, LDL; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000378:metabolism* / Q000628:therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases