Plasma Endothelin-1 (ET-1) is a useful marker for early renal dysfunction in a general population

内皮素-1（ET-1）是一种来源于内皮细胞的强有力的血管收缩剂。一些少数人类研究显示高血压患者血浆ET-1水平较高，但其他研究则不然。此外，已在少数受试者中显示，尿毒症患者中ET-1升高。然而，ET-1水平是否与肾功能不全有关，尚未见流行病学调查。1999年，共有1 492人接受了健康检查。空腹ET-1的数据为1，450。采用放射免疫法测定血浆ET-1水平。我们还测量了BMI、收缩压和舒张压（BP）、血红蛋白A_<1c>、胆固醇、BUN、肌酐和尿酸。采用Cockcroft-Gault公式计算肌酐清除率，以评估肾功能：[（140-年龄）×体重（kg）]/[72×血清肌酐]（女性为×0.85）。采用问卷调查的方法评价吸烟习惯。男性平均ET-1为4.93±1.73pg/ml，女性为4.84±1.54pg/ml。平均肾小球滤过率（GFR）男性为69.9±20.7ml/min，女性为65.3±18.6ml/min。ET-1与GFR呈强负相关（p&lt;0.001）。在控制了与ET-1关系最密切的年龄后，这种关联仍然显著。为了进一步研究血浆ET-1水平与GFR之间的关系，我们进行了协方差分析。按GFR五分位数分层的平均ET-1，经年龄、性别和吸烟调整，与ET-1显著相关。ET-1与GFR呈线性负相关（P=0.03）。我们的数据表明，在流行病学研究中，ET-1升高是肾功能不全的一个有用的标志物。

Endothelin-1 (ET-1) is a potent vasoconstrictor derived from the endothelium. Several studies with a small number in humans showed high plasma ET-1 levels in hypertension but did not so in other studies. Furthermore, it has been shown in a small number of subjects that ET-1 is elevated in uremic patients. However, there have been no epidemiological surveys as to whether ET-1 level is related to renal dysfunction. A total of 1,492 subjects received a health examination in 1999. The data for fasting ET-1 of 1,450 were obtained. A specific radioimmunoassay was used to measure ET-1 levels. We also measured BMI, systolic and diastolic blood pressure (BP), hemoglobin A_<1c>, cholesterol, BUN, creatinine, and uric acid. Creatinine clearance was calculated by the Cockcroft-Gault formula for assessing kidney function : [(140-age)×weight(kg)]/[72×serum creatinine](×0.85 for women). Smoking habit was evaluated by questionnaire. Mean ET-1 was 4.93±1.73pg/ml in men and 4.84±1.54pg/ml in women. Mean glomerular filtration rate (GFR) was 69.9±20.7ml/min in men and 65.3±18.6ml/min in women. ET-1 showed a strong inverse association (p<0.001) with GFR. After controlling for age, which is the strongest relation to ET-1, the association remained significant. In order to further examine the association between plasma ET-1 levels and GFR, we performed analysis of covariance. The mean ET-1 stratified by quintiles of GFR adjusted for age, sex and smoking, which is significantly associated with ET-1. There was a linear and significant inversely trend (p=0.03) between ET-1 and GFR. Our data suggest that elevated ET-1 is a useful marker for renal dysfunction in an epidemiological study.