In contrast to
proteins and
lipids, oxidative damage to
DNA has not been well studied in patients undergoing
hemodialysis (HD). We hypothesized that phagocytes are activated after blood-membrane contact during HD, and
oxidants from metabolic activation can damage leukocyte
DNA. To test this hypothesis, the
8-hydroxy-2'-deoxyguanosine (8-OHdG) content of leukocyte
DNA was measured by high-performance liquid chromatography electrochemical detection method in 35 age- and sex-matched healthy subjects, 22 undialyzed patients with advanced
renal failure, and 109 HD patients to assess the relation between oxidative DNA damage and
complement-activating membranes, blood
antioxidants, and
iron status. Dialysis membranes were classified into
complement-activating (
cellulose; n = 55) and non-
complement-activating (
polymethylmethacrylate [
PMMA]; n = 35;
polysulfone [PS]; n = 19) membranes. We found increased oxidative stress in undialyzed and HD patients based on a decrease in plasma levels of ascorbate and
alpha-tocopherol adjusted for blood
lipid (
alpha-tocopherol/
lipid),
serum albumin, and
reduced glutathione levels in whole blood and an increase in
oxidized glutathione levels in whole blood compared with controls (P < 0.001). The greatest 8-OHdG level in leukocyte
DNA was in HD patients, followed by undialyzed patients and healthy controls (P < 0.001), and was significantly greater in HD patients using
cellulose membranes than those using
PMMA or PS membranes (P < 0.001). 8-OHdG levels correlated with plasma
alpha-tocopherol/
lipid (r = -0.314; P < 0.005), serum
iron (r = 0. 446; P < 0.001), and
transferrin saturation values (r = 0.202; P < 0.05) in the analysis of all HD patients. In a 6-week crossover study, 8-OHdG levels significantly decreased after the switch from
cellulose to synthetic membranes for 2 weeks and increased after the shift from synthetic to
cellulose membranes (P < 0.05).
Iron metabolism indices and plasma
alpha-tocopherol/
lipid values did not change significantly in the study period. We conclude that 8-OHdG content in leukocyte
DNA is a
biomarker of
oxidant-induced DNA damage in HD patients. Oxidative DNA damage is a consequence of
uremia, further augmented by
complement-activating membranes.