Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden.
Division of Nephrology, Department of Medicine, Showa University School of Medicine Tokyo, Tokyo, Japan.
Eur J Intern Med. 2019 Oct;68:60-65. doi: 10.1016/j.ejim.2019.07.035. Epub 2019 Aug 9.
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.
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.
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 (95% confidence interval) 1.17 (1.08-1.26), remained essentially unchanged when adjusting also for inflammation in three separate models including: hsCRP, RR = 1.15 (1.06-1.25); IL-6, RR = 1.15 (1.07-1.25); and TNF, RR = 1.16 (1.07-1.26).
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.
氧化应激和低度全身炎症是慢性肾脏病（CKD）的常见相关后遗症，与死亡率有关。我们研究了血清 8-羟基-2'-脱氧鸟苷（8-OHdG），一种氧化 DNA 损伤的标志物，与 CKD 个体死亡率之间的关系，并分析了炎症是否改变了这种关系。
在 376 名肾小球滤过率（eGFR）范围广泛的个体中；>60ml/min（n=53）、15-60ml/min（n=60）和<15ml/min（n=263），通过 ROC 曲线确定血清 8-OHdG、高敏 C 反应蛋白（hsCRP）、白细胞介素-6（IL-6）和肿瘤坏死因子（TNF）的截断值作为死亡率的预测因子。我们通过多元广义线性模型分析了 8-OHdG 与炎症标志物的关系，以及 hsCRP、IL-6 和 TNF 对 8-OHdG 与全因死亡率之间关联的重叠效应。
在单独的个体暴露分析中，较高的 8-OHdG、hsCRP 和 IL-6（但不是 TNF）在调整年龄、性别、糖尿病、心血管疾病、蛋白质能量消耗、队列日历年份、血样储存时间和 eGFR 等因素的多变量模型中，均与死亡风险增加独立相关。对于 8-OHdG，当在三个单独的模型中也调整炎症时，多元相对风险比，RR（95%置信区间）1.17（1.08-1.26），RR 基本保持不变，三个模型包括：hsCRP，RR=1.15（1.06-1.25）；IL-6，RR=1.15（1.07-1.25）；和 TNF，RR=1.16（1.07-1.26）。
血清 8-OHdG，一种氧化 DNA 损伤的生物标志物，与 eGFR 广泛范围内的个体全因死亡率风险增加相关，这种关联独立于炎症。
