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

Am J Kidney Dis. 2000 Nov;36(5):934-44. doi: 10.1053/ajkd.2000.19086.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Biomarkers / blood
  • Case-Control Studies
  • Complement Activation
  • Cross-Over Studies
  • DNA / chemistry*
  • DNA Damage*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / blood*
  • Female
  • Glutathione / blood
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / therapy
  • Leukocytes / chemistry
  • Male
  • Membranes, Artificial*
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress / genetics*
  • Renal Dialysis* / adverse effects


  • Biomarkers
  • Membranes, Artificial
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Deoxyguanosine
  • Glutathione