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.
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.
Hara
Taiga
T
Department of CardioRenal and Cerebrovascular Medicine, Faculty of medicine, Kagawa University, Kagawa, Japan.
Kiyomoto
Hideyasu
H
Hitomi
Hirofumi
H
Moriwaki
Kumiko
K
Ihara
Genei
G
Kaifu
Kumiko
K
Fujita
Yoshiko
Y
Higashiyama
Chikako
C
Nishiyama
Akira
A
Kohno
Masakazu
M
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*
D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases