Does Sodium Affect Endothelial Function in Individuals With Chronic Kidney Disease?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Under conditions of high (vs. low sodium intake) ...
研究概览
简要总结
Heart disease and stroke, known as cardiovascular disease, are major causes of death in people with chronic kidney disease. Abnormalities of a metabolic pathway called the "L-arginine-nitric oxide" pathway are thought to be particularly important in these people, and previous research in animals has suggested that sodium (salt) affects part of this metabolic pathway. The purpose of our research is to study the effects of sodium intake on the "L-arginine-nitric oxide" pathway, and on blood vessel function, in patients with kidney disease.
详细描述
Chronic kidney disease (CKD) is associated with abnormalities of endothelial function (EF) and nitric oxide (NO) synthesis, and it is proposed that the endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) plays a central role. In man ADMA is largely metabolized by dimethylarginine dimethylaminohydrolase (DDAH), with some renal excretion occurring. Sodium inhibits DDAH expression in experimental animals and, given that CKD is frequently characterized by sodium retention, it would be interesting to study the effects of sodium loading on DDAH activity/expression, ADMA levels and EF in CKD patients.
To answer these questions, we have designed a double-blind cross-over study employing Slow Sodium (150 mmol/day) and placebo for seven days in individuals with mild-to-moderate CKD. Changes in the ratio of urinary ADMA to dimethylamine (DMA, an ADMA metabolite) will be used as an marker of DDAH activity/expression. ADMA will be measured by ELISA, DMA by high performance liquid chromatography, and EF by venous occlusion plethysmography.
We propose to test the following hypothesis; that in subjects with mild-to-moderate CKD under conditions of high sodium intake, as compared to low-normal sodium intake:
(i) The ratio [ADMA]urine:[DMA]urine is increased (ii) [ADMA]plasma is increased (iii) Endothelium-dependent vasodilatation is reduced
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CKD Stages 2 and 3 [= calculated creatinine clearance of 30 to 89 ml/min/1.73m2 by Cockcroft-Gault formula]
- •18 to 75 years old
排除标准
- •>3 g/24 hours of proteinuria
- •Uncontrolled hypertension (systolic BP >160 mmHg, diastolic BP >100 mmHg on/off anti-hypertensive medication)
- •Diabetes mellitus
- •Tobacco smoking
- •Total fasting cholesterol >6 mmol/L
- •Uncontrolled heart failure or active IHD
- •Chronic liver failure
- •Active malignancy
结局指标
主要结局
Under conditions of high (vs. low sodium intake) ...
(i) The ratio [ADMA]urine:[DMA]urine is increased
(ii) [ADMA]plasma is increased
(iii) Endothelium-dependent vasodilatation is reduced
次要结局
未报告次要终点