Impaired renal function and duration of dialysis therapy are associated with oxidative stress and proatherogenic cytokine levels in patients with end-stage renal disease

Objectives: The present study was undertaken to clarify the role of the impaired renal function and the dialysis therapy on plasma levels of proatherogenic cytokines and Cu/Zn superoxide dismutase (Cu/Zn SOD)-as a marker of oxidative stress (SOX) in uraemia. Design and methods: We have measured the levels of Cu/Zn SOD, monocyte chemoattractant protein-1 (MCP-1) macrophage inflammatory proteins (HP-1 alpha, MIP-1 beta) and vascular endothelial growth factor (VEGF) in the plasma of predialysis (CRF) (n=42), on maintenance hemodialysis (HD) (n=25) or peritoneal dialysis (PD) (n=45) patients and in the healthy volunteers (n=20). Results: The increase in Cu/Zn SOD levels was in PD and HD patients compared to controls (215.56 +/- 125.18 and 356.28 +/- 122.57 versus 53.53 +/- 23.65 ng/ml, respectively). In plasma of the CRF, PD and HD subjects we have also observed the significant increase in the levels of MIP-1 beta [31.5 (2-149) 33.0 (1-203) and 76.0 (9-345), respectively]; MCP-1 (616.50 +/- 240.15, 943.64 +/- 348.99 and 968.50 +/- 355.85, respectively) and VEGF (387.93 +/- 184.63, 371.56 +/- 125.18 and 645.56 +/- 136.30, respectively) compared to healthy people. In the predialysis group, creatinine clearance correlated with Cu/Zn SOD and cytokine levels. Moreover, the cytokine levels were also associated with age. In dialysis patients, the correlations were between duration of dialysis treatment and both Cu/Zn SOD and cytokine levels. There was also a direct relationship between Cu/Zn SOD and both MIP-1 beta and VEGF levels. Conclusions: This study has shown that impaired renal function, age and duration of dialysis treatment are associated with increased oxidative stress and proatherogenic cytokine levels in uremic patients. (c) 2006 The Canadian Society of Clinical Chemists. All rights reserved.