Oxidative DNA damage and mortality in hemodialysis and peritoneal dialysis patients.

Abstract

Increased oxidative stress in dialysis patients is thought to contribute to increased mortality; however, confirmatory data are scarce. We analyzed the serum concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, in relation to mortality in hemodialysis (HD) and peritoneal dialysis (PD) patients. Serum 8-OHdG, interleukin 6 (IL-6), other biochemical markers, Davies comorbidity score, and protein-energy wasting (PEW) were assessed in 303 prevalent patients treated with HD (n = 220; age: 63 ± 14 years) or PD (n = 83; age: 64 ± 14 years). Mortality was assessed after a median follow-up of 31 months. The median (25th - 75th percentile) concentration of 8-OHdG was higher in HD than in PD patients: 1.3 ng/mL (0.9 - 1.8 ng/mL) versus 0.5 ng/mL (0.4 - 0.6 ng/mL), p < 0.001. The HD modality (standard β = 0.57, p < 0.001) and dialysis vintage (standard β = 0.12, p = 0.02) were independent predictors of serum 8-OHdG in a multivariable linear regression model including age, sex, body mass index, dialysis modality (HD or PD), preceding time on dialysis (dialysis vintage), PEW, comorbidity score, IL-6, and use of angiotensin converting-enzyme inhibitors or angiotensin II receptor blockers or statins. During follow-up, 107 patients died. In multivariable Cox regression models including all 303 patients and adjusted for age, sex, body mass index, dialysis modality, dialysis vintage, and comorbidity score, 8-OHdG was significantly associated with all-cause mortality (adjusted hazard ratio: 1.40; 95% confidence limits: 1.05, 1.87 for 1 standard deviation increase of 8-OHdG). In subgroup analyses according to dialysis modality, 8-OHdG was associated with mortality in HD patients but not in PD patients. Oxidative stress as assessed by 8-OHdG is an independent predictor of all-cause mortality in dialysis patients. This association was seen in HD patients, but no such association could be demonstrated for PD patients.