Oxidative stress on DNA in chronic renal failure: The influence of different hemodialysis membranes

It has been reported that uremia is a state of oxidative stress and may play an important role as a pathological cause of various uremic complications. Oxidative stress is known to increase conversion of deoxyguanosine to 8-hydroxy-2-deoxyguanosine (8-OHdG) in DNA, and 8-OHdG is used as a marker of oxidative DNA damage. We evaluated plasma and urinary concentrations of 8-OHdG in 49 patients (male 28, female 21; mean age 65 years; diabetic 27, nondiabetic 22) with chronic renal disease (CRD) and 22 patients (male 14, female 8; mean age 63 year; diabetic 7, nondiabetic 15) on maintenance hemodialysis (M-HD). Plasma concentrations of 8-OHdG were measured using a highly sensitive ELISA kit, and the urinary mean concentrations of 8-OHdG were measured using an ELISA kit. Plasma concentrations of creatinine (Cr), Urea nitrogen (UN), and β2-microgloblin (β2-MG) and 24-h creatinine clearance (CCr) were also measured in CRD patients. Furthermore, 8-OHdG was measured before the dialysis session in M-HD patients. The plasma concentration of 8-OHdG in patients on CRD was significantly correlated with serum-creatinine (S−Cr), serum-umea nitrogen (S-UN), and β-MG (P<0.0001) and also significantly negatively correlated with CCr (P<0.005), but was not significantly correlated with age, fasting blood suger (FBS), hemoglobin A1C (HbA1C), and urinary concentration of 8-OHdG were not correlated with S-Cr, S-UN, β2-MG, and CCr. The plasma mean concentrations of 8-OHdG in patients on CRD and M-HD were as follows: CRD (CCr>50 ml/min,n=12), 0.108±0.41 ng/ml; CRD (CCr<10 ml/min,n=9), 0.277±0.15 ng/ml; M-HD (n=22), 0.217±0.59 ng/ml (mean±SD). The mean plasma concentration of 8-OHdG was 0.296 ±0.75 ng/ml in patients on M-HD in the polysulfone mem-brane group, 0.304±0.122 ng/ml their cellulose membrane group, and 0.354±0.21 ng/ml their vitamin E-modified cellulose membrane group. This study showed that in CRD patients, oxidative stress on DNA increasesed with the progression of renal disease, and that end-stage CRD patients were already exposed to the same degree of oxidative stress on DNA as M-HD patients. In M-HD patients, oxidative stress on DNA was not related to the type of hemodialysis membrane.