Department of Renal Medicine, Royal Derby Hospital, Derby, United Kingdom.
Clin J Am Soc Nephrol. 2011 Oct;6(10):2389-94. doi: 10.2215/CJN.11211210. Epub 2011 Aug 18.
Endotoxin (ET) is recognized to cause adverse effects on cardiovascular (CV) structure. Circulatory translocation of gut bacterial ET is described in heart failure. Chronic kidney disease (CKD) is common in older people and aggressive BP control is the cornerstone of management. We therefore studied ET after improvement of the overall CV milieu with introduction of optimized antihypertensive therapy (AHT).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We recruited 40 hypertensive nondiabetic patients (≥70 years) with CKD stages 3 and 4 and hypertensive non-CKD matched controls. Assessment was performed after complete AHT washout and repeated after AHT reintroduction to target BP 130/80 mmHg. Pulse wave velocity (PWV) and analysis were assessed by applanation tonometry, central hemodynamics by continuous digital pulse wave analysis, vascular calcification (VC) by superficial femoral artery CT, and serum ET by Limulus Amebocyte assay.
Mean age was 76 ± 5 years, estimated GFR (eGFR) (CKD group) was 40 ± 14 ml/min per 1.73 m(2), and achieved BP was 128/69 mmHg. Washout ET was 0.042 ± 0.011 EU/ml and was independent of renal function, gender, age, BP, VC, arterial stiffness, and high-sensitivity C-reactive protein. ET significantly decreased with AHT (to 0.020 ± 0.028 EU/ml; P < 0.001) and was associated with eGFR (R = -0.38; P = 0.02), arterial wave reflection (Augmentation Index R = -0.42; P = 0.01), and degree of tonic vasodilatation (total peripheral resistance R = -0.37; P = 0.03), but not VC, PWV, gender, age, BP, or high-sensitivity C-reactive protein.
Elderly patients with hypertension have elevated serum ET. Improvement of their CV status with optimized AHT is associated with a significant reduction in endotoxemia. Further investigation of the potential pathophysiological mechanisms linking CV disease and CKD with this previously unappreciated effect of AHT appears warranted.
内毒素（ET）被认为会对心血管（CV）结构造成不良影响。肠道细菌 ET 的循环移位在心力衰竭中已有描述。慢性肾脏病（CKD）在老年人中很常见，积极控制血压是管理的基石。因此，我们研究了在引入优化降压治疗（AHT）改善整体 CV 环境后 ET 的变化。
设计、地点、参与者和测量方法：我们招募了 40 名患有 CKD 3 期和 4 期的高血压非糖尿病患者（≥70 岁）和高血压非 CKD 匹配对照者。在完全停用 AHT 后进行评估，并在重新引入 AHT 以达到目标血压 130/80mmHg 后再次进行评估。通过平板测压法评估脉搏波速度（PWV）和分析，通过连续数字脉搏波分析评估中心血流动力学，通过股浅动脉 CT 评估血管钙化（VC），通过鲎变形细胞溶解物试验评估血清 ET。
平均年龄为 76±5 岁，估算肾小球滤过率（eGFR）（CKD 组）为 40±14ml/min/1.73m2，达到的血压为 128/69mmHg。洗脱 ET 为 0.042±0.011EU/ml，与肾功能、性别、年龄、血压、VC、动脉僵硬度和高敏 C 反应蛋白无关。AHT 后 ET 显著降低（至 0.020±0.028EU/ml；P<0.001），与 eGFR（R=-0.38；P=0.02）、动脉波反射（增强指数 R=-0.42；P=0.01）和紧张性血管舒张程度（总外周阻力 R=-0.37；P=0.03）相关，但与 VC、PWV、性别、年龄、血压或高敏 C 反应蛋白无关。
患有高血压的老年患者血清 ET 升高。用优化 AHT 改善 CV 状态与内毒素血症的显著降低有关。进一步研究这种以前未被认识到的 AHT 作用与 CV 疾病和 CKD 之间的潜在病理生理机制似乎是合理的。
