Inflammation, Oxidative Stress and Atherosclerosis in Chronic Renal Failure Patients

Document Type : Original Article

Authors

1 Medical Biochemistry Department, Faculty of Medicine. Assuit University

2 Internal Medicine Department, Faculty of Medicine. Assuit University

3 Radiology Department, Faculty of Medicine. Assuit University

Abstract

Background: Accelerated atherosclerosis is the major cause of mortality in patients
on chronic hemodialysis (HD). Inflammation, increased oxidative stress and
endothelial activation or dysfunction might be the major factors leading to high
cardiovascular mortality rate in HD patients. Also, C667T mutation of
methylenetetrahydrofolate reductase (MTHFR) might be associated with accelerated
atherosclerosis. Aim: The present study was designed to clarify the role of
inflammation, oxidative stress parameters, endothelial activation or dysfunction and
genotyping of MTHFR enzyme which affect the level of homocysteine and their
relation to carotid artery intima-media thickness (CIMT) as indicators of
atherosclerosis. Subjects & Methods: 44 chronic hemodialysis (HD) patients and 40
healthy subjects were included in the study. Serum highly sensitive C reactive protein
(hs-CRP) and IL-6 were measured as inflammatory markers, soluble vascular cell
adhesion molecule-1 (sVCAM-1) was measured as a marker of endothelial activation
and dysfunction. Serum thiobarbituric acid reactive substances (TBARS), total nitric
oxide (NO), total peroxides (TP), total antioxidant capacity (TAC) and oxidative
stress index (OSI) levels were determined as oxidative stress markers. Common
carotid intima media thickness (CC-IMT) was assessed by carotid artery
ultrasonography, genotyping of MTHFR enzyme which affect the level of
homocysteine was analyzed by PCR –RFLIP technique. Results: Chronic HD patients
had elevated levels of inflammatory markers (hs-CRP and IL-6), enhanced
endothelial activation or dysfunction demonstrated by elevated VCAM-1 as compared
by healthy controls. Also, they had enhanced oxidative stress indicated by the higher
levels of NO, TBARS, TP, OSI and lower levels of TAC as compared to controls.
Hemodialysis patients had significantly higher CC-IMT levels. There is a significant
positive correlation between inflammatory cytokines (hs-CRP and IL-6), and each of
TBARS, total NO, TP and OSI with CC-IMT Also, the previous parameters negatively
correlated with TAC. There is no significant difference in the genotype of C667T
MTHFR between patients and controls, but that mutation especially the TT genotype
is associated with development of atherosclerosis as indicated by the increase of CCIMT.