Bicarbonate Administration in CKD

CKD 中碳酸氢盐的管理

• 批准号: 9324442
• 负责人: Jessica B Kendrick
• 金额: $ 44.85万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9324442
• 关键词: Acidosis; Acids; Alkalies; Alkaline Phosphatase; Arteries; Bicarbonates; Blood Vessels; Bone Diseases; C-terminal; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chronic Kidney Failure; Clinical Trials; Collagen Type I; Complication; Data; Development; Diet; Disease Progression; Double-Blind Method; Endothelin-1; Endothelium; Equilibrium; Functional disorder; Gadolinium; General Population; Goals; Health; Heart; Heart failure; Human; Hypertension; Inflammation; Intervention Trial; Kidney; Kidney Diseases; Laboratories; Left Ventricular Hypertrophy; Left Ventricular Mass; Left ventricular structure; Link; Magnetic Resonance Imaging; Measures; Mediating; Metabolic acidosis; N-terminal; Observational Study; Oral; Outcome; Patients; Physicians; Physiologic pulse; Placebo Control; Placebos; Population; Procedures; Randomized; Recommendation; Reporting; Research; Risk; Risk Factors; Serum; Sodium Bicarbonate; Staging; Surrogate Markers; Testing; Time; Vascular calcification; Vasoconstrictor Agents; arterial stiffness; base; bone; bone loss; bone metabolism; bone turnover; brachial artery; calcification; calcium phosphate; clinical practice; endothelial dysfunction; gadolinium oxide; improved; indexing; mortality; novel; novel marker; novel therapeutics; patient population; prospective; randomized trial; trial comparing; week trial

PROJECT SUMMARY/ABSTRACT Metabolic acidosis, reflected by a lower serum bicarbonate level, 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. Acidosis increases inflammation, induces endothelin-1 (a potent vasoconstrictor) and increases calcium and phosphate efflux from bone, all of which are risk factors for arterial dysfunction and LVH. 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, 52 week 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 52 weeks 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 52 weeks of sodium bicarbonate therapy or placebo. In Aim 3, we will compare changes over time in a novel test of calcification that provides a measure of the overall calcification propensity of serum (T50) and in markers of bone metabolism (bone specific alkaline phosphatase, beta C-terminal telopeptide, and N-terminal propeptide of type 1 collagen) after 52 weeks 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.

项目总结/摘要 代谢性酸中毒是慢性肾脏病的常见并发症，表现为血清碳酸氢盐水平降低。 慢性肾脏病（CKD）是一种慢性肾脏病，因为患病的肾脏不能排泄每日的饮食酸负荷。降低血清 碳酸氢盐水平，即使在正常的实验室范围内，也与高血压的风险密切相关， 心血管疾病（CVD）、CKD进展和死亡。动脉功能障碍在病程早期就开始了 肾脏疾病，是一个关键因素，负责左心室肥大（LVH）的发展， 人口LVH是CKD患者心血管死亡率的最强预测因子。酸中毒会增加炎症， 诱导内皮素-1（一种有效的血管收缩剂）并增加钙和磷酸盐从骨中流出，所有这些都是 这是动脉功能障碍和LVH的危险因素。小型干预性试验表明， 与碱治疗减缓肾脏疾病的进展，即使在患者血清碳酸氢盐水平正常。 由于CVD和CKD进展的风险因素经常重叠，因此碱疗法在生物学上是合理的， CKD患者的心血管结局也可能得到改善。在我们的初步数据中，碱疗法 改善16例CKD 3-4期患者的血管内皮功能。因此，碱疗法 可能代表CKD的廉价和新颖的治疗范例。我们提出了一个随机的， 一项在108例3-4期CKD患者中进行的双盲、安慰剂对照、52周试验，旨在检查 碳酸氢钠治疗对CVD替代指标的影响。我们的总体假设是， 碳酸氢盐将改善CKD 3-4期患者的血管功能和LVH指标。我们的首要 目的是确定碱疗法对改善血管内皮功能和减少大血管病变的疗效。 使用非侵入性手术对CKD 3-4期患者的弹性动脉硬度进行研究。在目标1中，我们比较 52周后肱动脉血流介导的扩张和主动脉脉搏波速度随时间的变化 碳酸氢钠治疗或安慰剂。在目标2中，我们将比较LVMI随时间的变化， 无钆心脏磁共振成像，碳酸氢钠治疗52周后，或 安慰剂在目标3中，我们将在一种新的钙化测试中比较随时间的变化， 血清（T50）和骨代谢标志物（骨特异性碱性磷酸酶）的总体钙化倾向 磷酸酶，β C-末端肽和1型胶原的N-末端前肽）。 碳酸氢钠治疗或安慰剂。这项新研究的结果有可能为临床提供信息。 通过提供必要的证据来建立碳酸氢钠治疗作为一种廉价的， 易于管理的选择，用于治疗CKD 3-4期患者的动脉功能障碍。