8-hydroxy-2 '-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in chronic hemodialysis patients

In contrast to proteins and lipids, oxidative damage to DNA has not been we ll studied in patients undergoing hemodialysis (HD), We hypothesized that p hagocytes are activated after blood-membrane contact during HD, and oxidant s from metabolic activation can damage leukocyte CDNA. To test this hypothe sis, the 8-hydroxy-2'-deoxyguanosine (8-OHdG) content of leukocyte DNA was measured by high-performance liquid chromatography electrochemical detectio n method in 35 age- and sex-matched healthy subjects, 22 undialyzed patient s with advanced renal failure, and 109 HD patients to assess the relation b etween oxidative DNA damage and complement-activating membranes, blood anti oxidants, and iron status. Dialysis membranes were classified into compleme nt-activating (cellulose; n = 55) and non-complement-activating (polymethyl methacrylate [PMMA]; n = 35; polysulfone [PS]; n = 19) membranes, We found increased oxidative stress in undialyzed and HD patients based on a decreas e in plasma levels of ascorbate and alpha -tocopherol adjusted for blood li pid (alpha -tocopherol/lipid), serum albumin, and reduced glutathione level s in whole blood and an increase in oxidized glutathione levels in whole bl ood compared with controls (P < 0.001), The greatest 8-OHdG level in leukoc yte DNA was in MD patients, followed by undialyzed patients and healthy con trols (P < 0.001), and was significantly greater in HD patients using cellu lose membranes than those using PMMA or BS membranes (P < 0.001), 8-OHdG le vels 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 crossove r study, 8-OHdG levels significantly decreased after the switch from cellul ose to synthetic membranes for 2 weeks and increased after the shift from s ynthetic to cellulose membranes (P < 0.05). Iron metabolism indices and pla sma alpha -tocopherol/lipid values did not change significantly in the stud y period. We conclude that 8-OHdG content in leukocyte DNA is a biomarker o f oxidant-induced DNA damage in HD patients. Oxidative DNA damage is a cons equence of uremia, further augmented by complement-activating membranes. (C ) 2000 by the National Kidney Foundation, Inc.