Bicarbonate Administration In CKD

CKD 中碳酸氢盐的管理

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要酸潴留是慢性肾脏病 (CKD) 的常见并发症，因为患病的肾脏无法排出每日膳食酸负荷。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。动脉功能障碍在肾脏疾病的早期就开始出现，是导致肾病发展的关键因素。该人群存在左心室肥厚 (LVH)。 LVH 是心血管死亡率最强的预测因子慢性肾病。酸潴留导致血管紧张素 II、内皮素-1 和醛固酮的产生依次增加以增强尿酸排泄。这三种体液因素都直接或间接诱发内皮功能障碍、血管僵硬度、左心室肥厚和血管钙化。小型介入试验研究表明，碱疗法可以减缓肾脏疾病的进展，即使对于正常的患者也是如此。血清碳酸氢盐水平。由于 CVD 和 CKD 进展的危险因素经常重叠，因此从生物学角度来说 CKD 患者的碱治疗也可能改善心血管结局，这似乎是合理的。在我们的初步数据显示，碱疗法改善了 16 名 CKD 3-4 期患者的血管内皮功能。因此，碱疗法可能代表 CKD 的一种廉价且新颖的治疗范例。我们提议对 108 名 CKD 患者进行一项为期 12 个月的随机、双盲、安慰剂对照试验第 3-4 阶段检查碳酸氢钠治疗对 CVD 替代指标的影响。我们的整体假设碳酸氢盐治疗将改善患者的血管功能和 LVH 指标 CKD 3-4 阶段。我们的主要目标是确定碱疗法改善血管的功效使用无创技术改善 CKD 3-4 期患者的内皮功能并降低大弹性动脉僵硬度程序。在目标 1 中，我们将比较肱动脉血流介导的扩张和主动脉血流随时间的变化。碳酸氢钠治疗或安慰剂 12 个月后的脉搏波速度。在目标 2 中，我们将比较 12 小时后，通过无钆心脏磁共振成像测量 LVMI 随时间的变化几个月的碳酸氢钠治疗或安慰剂。在目标 3 中，我们将比较体液随时间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，可测量总体钙化倾向碳酸氢钠治疗或安慰剂 12 个月后的血清（T50）。这项新颖的研究结果通过提供必要的证据来确定碳酸氢钠，有可能为临床实践提供信息治疗作为治疗患者动脉功能障碍的一种廉价且易于管理的选择 CKD 3-4 阶段。