Serum 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, is associated with mortality independent of inflammation in chronic kidney disease

Abstract

Background: Oxidative stress and low-grade systemic inflammation are common interrelated sequelae of chronic kidney disease (CKD) that associate with mortality. We investigated the association of serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, with mortality in CKD individuals and analyzed whether inflammation modifies the association.

Methods: In 376 individuals with a wide range of estimated glomerular filtration rate (eGFR); >60 ml/min (n = 53), 15-60 ml/min (n = 60) and <15 ml/min (n = 263), cut-off values of serum 8-OHdG, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF) as predictors of mortality were determined by ROC curves. We analyzed associations of 8-OHdG with inflammation markers and the overlapping effect of hsCRP, IL-6 and TNF on the association between 8-OHdG and all-cause mortality by multivariate generalized linear models.

Results: In separate individual exposure analyses, higher 8-OHdG, hsCRP, and IL-6 (but not TNF) were each independently associated with increased risk of death in multivariate models adjusted for age, sex, diabetes mellitus, cardiovascular disease, protein-energy wasting, cohort calendar year, blood sample storage time and eGFR. For 8-OHdG, the multivariate relative risk ratio, RR_8-OHdG (95% confidence interval) 1.17 (1.08-1.26), remained essentially unchanged when adjusting also for inflammation in three separate models including: hsCRP, RR_8-OHdG = 1.15 (1.06-1.25); IL-6, RR_8-OHdG = 1.15 (1.07-1.25); and TNF, RR_8-OHdG = 1.16 (1.07-1.26).

Conclusions: Serum 8-OHdG, a biomarker of oxidative DNA damage, is associated with increased all-cause mortality risk in individuals with a wide range of eGFR and this association is independent of inflammation.

Keywords: Chronic kidney disease; Dialysis; Inflammation; Mortality; Oxidative stress.