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).

CONCLUSION

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.

Copyright 2004 S. Karger AG, Basel