Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore, Maryland.
Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
J Am Geriatr Soc. 2018 Apr;66(4):804-811. doi: 10.1111/jgs.15268. Epub 2018 Jan 23.
To examine the hypothesis that the inflammatory state of aging is a risk factor for accelerated renal function (RF) decline using inflammatory biomarkers and RF measures collected over 9 years of follow-up in relatively healthy individuals enrolled in the Invecchiare in Chianti study.
Longitudinal.
Community.
Individuals aged 60 and older with baseline estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m and greater and no diabetes mellitus (DM) (N = 687).
eGFR, as a proxy for RF, was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at baseline and 3-, 6-, and 9-year follow-up. Incident chronic kidney disease (CKD) was defined as new-onset eGFR less than 60 mL/min per 1.73 m at each follow-up. Predictors included baseline and time-dependent inflammatory biomarkers: soluble tumor necrosis factor alpha receptors (sTNFα-R1 and -R2), interleukin (IL)-6, IL-18, IL-1β, IL-1 receptor antagonist, and high-sensitivity C-reactive protein.
Higher baseline sTNFα-R1 was significantly associated with lower eGFR over 9 years, independent of DM or blood pressure (baseline: β^ = -0.39, P = .001; 3-year: β^ = -0.26, P = .001; 6-year: β^ = -0.36, P = .001; 9-year: β^ = -0.47, P = .001). The rate of TNFα-R1 change was significantly associated with rate of eGFR change (β^ = -0.18, P = .001). Baseline sTNFα-R1 predicted incident CKD (per 1-standard deviation increment: 3-year: relative risk (RR) = 1.3, 95% confidence interval (CI) = 1.1-1.5; 6-year: RR = 1.5, 95% CI = 1.1-2.2; 9-year RR = 1.6, 95% CI = 1.1-2.2). Similar results were found for sTNFα-R2.
Baseline TNFα-R levels and their rates of change were significantly associated with RF decline and incident CKD in older adults independent of DM or blood pressure.
使用炎症生物标志物和在相对健康的个体中收集的肾功能 (RF) 下降的 9 年随访结果来检验衰老的炎症状态是加速 RF 下降的风险因素这一假说。
纵向研究。
社区。
基线估计肾小球滤过率 (eGFR) 为 60 mL/min/1.73 m 及以上且无糖尿病 (DM) 的 60 岁及以上个体 (N = 687)。
使用慢性肾脏病流行病学合作 (CKD-EPI) 方程在基线和 3、6 和 9 年随访时确定 eGFR，作为 RF 的替代指标。在每次随访时出现新的 eGFR 小于 60 mL/min/1.73 m 定义为新发慢性肾脏病 (CKD)。预测因素包括基线和时间依赖性炎症生物标志物：可溶性肿瘤坏死因子-α受体 (sTNFα-R1 和 -R2)、白细胞介素 (IL)-6、IL-18、IL-1β、IL-1 受体拮抗剂和高敏 C 反应蛋白。
基线 sTNFα-R1 较高与 9 年内 eGFR 降低显著相关，与 DM 或血压无关 (基线：β^ = -0.39，P =.001；3 年：β^ = -0.26，P =.001；6 年：β^ = -0.36，P =.001；9 年：β^ = -0.47，P =.001)。sTNFα-R1 的变化率与 eGFR 的变化率显著相关 (β^ = -0.18，P =.001)。基线 sTNFα-R1 预测 CKD 发生 (每增加 1 个标准差：3 年：相对风险 (RR) = 1.3，95%置信区间 (CI) = 1.1-1.5；6 年：RR = 1.5，95% CI = 1.1-2.2；9 年 RR = 1.6，95% CI = 1.1-2.2)。对于 sTNFα-R2 也得到了类似的结果。
基线 TNFα-R 水平及其变化率与老年人 RF 下降和 CKD 发生显著相关，与 DM 或血压无关。
