Boonprasert Kanyarat, Vesey David A, Gobe Glenda C, Ruenweerayut Ronnatrai, Johnson David W, Na-Bangchang Kesara, Satarug Soisungwan
Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
Centre for Kidney Disease Research, UQ Diamantina Institute and Centre for Health Services Research, Translational Research Institute, University of Queensland, Brisbane, Australia.
Clin Kidney J. 2018 Oct;11(5):681-687. doi: 10.1093/ckj/sfx153. Epub 2018 Feb 2.
Exposure to cadmium (Cd) has been associated with the development of hypertension, especially in women, but the mechanism of such an association is not understood. We hypothesize that Cd exposure alters renal production of 20-hydroxyeicosatetraenoic acid (20-HETE), which plays an indispensable role in renal salt balance and blood pressure control.
We examined long-term Cd exposure in relation to urinary 20-HETE excretion levels, tubular dysfunction and blood pressure measures, using data from a population-based, cross-sectional study that included 115 normotensive and 110 hypertensive women, 33-55 years of age, who lived in Cd contamination areas in Thailand.
The mean [standard deviation (SD)] blood Cd level of the study subjects was 3.57 (3.3) µg/L, while the mean (SD) urinary Cd and urinary 20-HETE levels were 0.58 (0.47) µg/g creatinine and 1651 (4793) pg/mL, respectively. Elevated 20-HETE levels were associated with a 90% increase in prevalence odds of hypertension (P = 0.029), four times greater odds of having higher urinary Cd levels (P = 0.030) and a 53% increase in odds of having higher levels of tubular dysfunction (P = 0.049), evident from an increase in urinary excretion of β2-microglobulin. In normotensive subjects, an increase in urinary 20-HETE levels from tertile 1 to tertile 3 was associated with a systolic blood pressure increase of 6 mmHg (95% confidence interval 0.3-12, P = 0.040).
This is the first report that links urinary 20-HETE levels to blood pressure increases in Cd-exposed women, thereby providing a plausible mechanism for associated development of hypertension.
镉（Cd）暴露与高血压的发生有关，尤其是在女性中，但这种关联的机制尚不清楚。我们推测，镉暴露会改变肾脏中20-羟基二十碳四烯酸（20-HETE）的生成，而20-HETE在肾脏盐平衡和血压控制中起着不可或缺的作用。
我们利用一项基于人群的横断面研究数据，研究长期镉暴露与尿20-HETE排泄水平、肾小管功能障碍和血压测量值之间的关系。该研究纳入了115名血压正常和110名高血压女性，年龄在33 - 55岁之间，她们生活在泰国的镉污染地区。
研究对象的平均血镉水平为3.57（3.3）μg/L，尿镉和尿20-HETE的平均水平分别为0.58（0.47）μg/g肌酐和1651（4793）pg/mL。20-HETE水平升高与高血压患病率增加90%相关（P = 0.029），尿镉水平升高的几率增加四倍（P = 0.030），肾小管功能障碍水平升高的几率增加53%（P = 0.049），这从β2微球蛋白尿排泄增加中明显可见。在血压正常的受试者中，尿20-HETE水平从第一三分位数增加到第三三分位数与收缩压升高6 mmHg相关（95%置信区间0.3 - 12，P = 0.040）。
这是第一份将尿20-HETE水平与镉暴露女性血压升高联系起来的报告，从而为高血压的相关发展提供了一个合理的机制。
