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 (MIP-1alpha, MIP-1beta) 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-1beta: [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-1beta 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.