Oxidative DNA damage and mortality in hemodialysis and peritoneal dialysis patients

Perit Dial Int. 2015 Mar-Apr;35(2):206-15. doi: 10.3747/pdi.2013.00259. Epub 2014 Mar 1.

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.

Keywords: End-stage renal disease; all-cause mortality; comorbidity; dialysis modality; oxidative stress.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aged
  • Biomarkers / blood
  • Cohort Studies
  • DNA Damage / physiology*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / blood
  • Female
  • Humans
  • Interleukin-6 / blood
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / mortality*
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Oxidative Stress / physiology*
  • Peritoneal Dialysis*

Substances

  • Biomarkers
  • Interleukin-6
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine