Bicarbonate Administration In CKD

CKD 中碳酸氢盐的管理

• 批准号: 9257176
• 负责人: Jessica B Kendrick
• 金额: $ 43.91万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9257176
• 关键词: Acids; Aldosterone; Alkalies; Angiotensin II; Arteries; Bicarbonates; Biological; Blood Vessels; Calcified; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chronic Kidney Failure; Clinical Trials; Complication; Data; Development; Diet; Disease Progression; Double-Blind Method; Endothelin-1; Endothelium; Equilibrium; Excretory function; Functional disorder; Gadolinium; Goals; Health; Heart Ventricle; Heart failure; Human; Hypertension; Intervention Trial; Kidney; Kidney Diseases; Laboratories; Left Ventricular Hypertrophy; Left Ventricular Mass; Left ventricular structure; Link; Magnetic Resonance Imaging; Measures; Mediating; Mediator of activation protein; Metabolic acidosis; Observational Study; Oral; Outcome; Patients; Physicians; Physiologic pulse; Placebo Control; Placebos; Plasma; Population; Procedures; Production; Randomized; Recommendation; Renin-Angiotensin-Aldosterone System; Reporting; Research; Risk; Risk Factors; Serum; Sodium Bicarbonate; Surrogate Markers; Testing; Time; Vascular Diseases; Vascular calcification; arterial stiffness; base; brachial artery; calcification; cardiovascular risk factor; clinical practice; endothelial dysfunction; improved; indexing; mortality; novel; novel marker; novel therapeutics; prospective; randomized trial; trial comparing; urinary

PROJECT SUMMARY/ABSTRACT Acid retention is a common complication of chronic kidney disease (CKD) as the diseased kidney is unable to excrete the daily dietary acid load. Lower serum bicarbonate levels, even within the normal laboratory range, are strongly linked to risks of hypertension, cardiovascular disease (CVD), CKD progression and death. Arterial dysfunction begins early in the course of kidney disease and is a key factor responsible for the development of left ventricular hypertrophy (LVH) in this population. LVH is the strongest predictor of cardiovascular mortality in CKD. Acid retention results in increased production of angiotensin II, endothelin-1 and aldosterone in order to enhance urinary acid excretion. All three of these humoral factors both directly and indirectly induce endothelial dysfunction, vascular stiffness, LVH and vascular calcification. Small interventional trials have shown that treatment with alkali therapy slows progression of kidney disease, even in patients with normal serum bicarbonate levels. Because risk factors for CVD and CKD progression often overlap, it is biologically plausible that alkali therapy in CKD patients may also result in improved cardiovascular outcomes. In our preliminary data, alkali therapy improved vascular endothelial function in 16 patients with CKD stage 3-4. Hence, treatment with alkali therapy may represent an inexpensive and novel therapeutic paradigm in CKD. We are proposing a randomized, double-blinded, placebo-controlled, 12-month trial of 108 patients with CKD stage 3-4 to examine the effect of sodium bicarbonate therapy on surrogate measures of CVD. Our overall hypothesis is that treatment with bicarbonate will improve indicators of vascular function and LVH in patients with CKD stage 3-4. Our primary goal is to determine the efficacy of alkali therapy for improving vascular endothelial function and reducing large elastic artery stiffness in patients with CKD stage 3-4 using noninvasive procedures. In Aim 1, we will compare changes over time in brachial artery flow-mediated dilation and aortic pulse wave velocity after 12 months of sodium bicarbonate therapy or placebo. In Aim 2, we will compare changes over time in LVMI, measured by gadolinium free cardiac magnetic resonance imaging, after 12 months of sodium bicarbonate therapy or placebo. In Aim 3, we will compare changes over time in humoral mediators of urinary acid excretion that promote vascular calcification (angiotensin II, endothelin-1 and aldosterone) and a novel test of calcification that provides a measure of the overall calcification propensity of serum (T50) after 12 months of sodium bicarbonate therapy or placebo. The results of this novel study have the potential to inform clinical practice by providing the necessary evidence to establish sodium bicarbonate therapy as an inexpensive and easy to administer option for the treatment of arterial dysfunction in patients with CKD stage 3-4.

项目摘要/摘要 酸保留是慢性肾脏疾病（CKD）的常见并发症，因为患病的肾脏无法 排泄每日饮食酸负荷。降低血清碳酸氢盐水平，即使在正常实验室范围内 与高血压，心血管疾病（CVD），CKD进展和死亡的风险密切相关。动脉 功能障碍始于肾脏疾病的早期，是负责发展的关键因素 该人群中的左心室肥大（LVH）。 LVH是心血管死亡率的最强预测指标 在CKD中。酸保留导致血管紧张素II，内皮素-1和醛固酮的产生增加 增强尿酸排泄。这三个这三个这些体液因素既直接和间接诱导 内皮功能障碍，血管刚度，LVH和血管钙化。小型介入试验有 表明使用碱疗法治疗减慢了肾脏疾病的进展，即使在正常患者中 血清碳酸氢盐水平。因为CVD和CKD进展的危险因素经常重叠，所以它在生物学上是 合理的CKD患者碱疗法也可能导致心血管结局改善。在我们的 初步数据，碱性疗法改善了16例CKD阶段3-4患者的血管内皮功能。 因此，碱疗法的治疗可能代表CKD中廉价且新颖的治疗范式。 我们提出了一项随机，双盲的，安慰剂对照的12个月试验，对108例CKD患者 第3-4阶段检查碳酸氢钠治疗对CVD替代措施的影响。我们的整体 假设是，用碳酸氢盐治疗将改善患者血管功能和LVH的指标 与CKD阶段3-4。我们的主要目标是确定碱疗法改善血管的功效 内皮功能并降低CKD阶段3-4患者的大型弹性动脉刚度使用非侵入性 程序。在AIM 1中，我们将比较臂动脉流介导的扩张和主动脉的随着时间的变化 碳酸氢钠治疗或安慰剂12个月后，脉搏波速度。在AIM 2中，我们将比较 LVMI的随着时间的变化，通过gadolinium noven gadolinium无心脏磁共振成像测量，12 碳酸氢钠疗法或安慰剂的月份。在AIM 3中，我们将比较随着时间的流逝的变化 促进血管钙化的尿酸排泄介质（血管紧张素II，内皮素-1和 醛固酮）和一种新颖的钙化测试，该测试提供了总体钙化倾向的度量 碳酸氢钠治疗或安慰剂12个月后，血清（T50）。这项新研究的结果具有 通过提供必要的证据来建立碳酸氢钠来为临床实践提供信息 治疗是一种廉价且易于管理的选择，用于治疗患者动脉功能障碍 与CKD阶段3-4。