Oxidative stress influences CC-chemokine levels in hemodialyzed patients.
BACKGROUND
Increased oxidative stress (SOX) has been reported in hemodialyzed (HD) patients, but its influence on CC-chemokine levels remains unknown.


METHODS
The levels of 3 distinct SOX markers (Cu/Zn superoxide dismutase (Cu/Zn SOD), total lipid peroxide, and autoantibodies against oxidized LDL (OxLDL-Ab)), as well as those of 4 CC-chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proteins (MIP-1alpha, MIP-1beta), regulated upon activation, normal T cell expressed and secreted (RANTES), and tumor necrosis factor-alpha (TNF-alpha)) were measured pre- and post-HD session in 15 HD patients with cardiovascular disease (CVD) and 12 HD patients without CVD (pre- and post-HD session) and 17 controls.


RESULTS
Cu/Zn SOD levels were elevated in HD patients (both before and after HD) compared to controls (p < 0.001). Total lipid peroxide levels were similar in the controls in pre-dialysis samples, but were increased after a HD session (p < 0.001). Pre-dialysis OxLDL-Ab levels were increased only in the HD group with CVD compared to controls (p < 0.05). The pre-dialysis plasma levels of TNF-alpha (p < 0.001), MCP-1 (p < 0.001) and MIP-1beta (p < 0.01) were increased both in all HD patients and subgroups with CVD when compared to the controls, and remained significantly elevated when measured after HD. Dialysis increased MCP-1 (p < 0.05) and MIP-1beta (p < 0.001) levels as compared to the controls as well as in patients without CVD. Plasma RANTES was significantly lower before HD (p < 0.05) and after HD (p < 0.001) in patients with CVD. Patients without CVD and all HD patients also had lower RANTES before and after HD when compared to controls (all p < 0.001). A positive correlation was observed between plasma pre-dialysis Cu/Zn SOD levels and the other SOX markers (all p < 0.05), age (p < 0.05) and duration of hemodialysis (p < 0.001). A positive relationship existed between plasma Cu/Zn SOD levels and those of MCP-1, MIP-1beta and TNF-alpha (all p < 0.001). RANTES levels negatively correlated with Cu/Zn SOD (p < 0.0001).TNF-alpha positively correlated with age (p < 0.05), total lipid peroxide (p = 0.010), MCP-1 (p < 0.01) and MIP-1beta levels (p < 0.01). An identifiable association exists between MCP-1 and MIP-1beta levels (p < 0.01), whereas both MCP-1 and MIP-1beta were inversely correlated with RANTES (both p < 0.05).


CONCLUSIONS
Our data indicate for the first time a probable functional relationship between oxidative stress and CC-chemokine levels in hemodialyzed patients, particularly in those with cardiovascular disease. This relationship may represent one of the mechanisms involved in the progression of atherosclerosis in these patients.
Pawlak
Krystyna
K
Department of Nephrology, Medical University, Bialystok, Poland. krystynapawlak@poczta.onet.pl
Pawlak
Dariusz
D
Mysliwiec
Michal
M
D001161:Arteriosclerosis / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology; D019742:Chemokines, CC / Q000097:blood*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D008054:Lipid Peroxides / Q000097:blood; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D006435:Renal Dialysis; D013482:Superoxide Dismutase / Q000097:blood
D001323:Autoantibodies; D015415:Biomarkers; D019742:Chemokines, CC; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D013482:Superoxide Dismutase