Hong Xu1, Makoto Watanabe2, Abdul Rashid Qureshi3, Olof Heimbürger3, Peter Bárány3, Björn Anderstam3, Monica Eriksson3, Peter Stenvinkel3, Bengt Lindholm3. 1. Department of Clinical Science, Intervention and Technology, Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, PR China. 2. Division of Nephrology, Department of Medicine, Showa University School of Medicine Tokyo, Tokyo, Japan. 3. Department of Clinical Science, Intervention and Technology, Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Abstract
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: The median (25th - 75th percentile) concentration of 8-OHdG was higher in HD than in PDpatients: 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 HDpatients but not in PDpatients. CONCLUSIONS: Oxidative stress as assessed by 8-OHdG is an independent predictor of all-cause mortality in dialysis patients. This association was seen in HDpatients, but no such association could be demonstrated for PDpatients.
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