Bicarbonate Administration In CKD

项目总结/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 排出每日饮食中的酸负荷。血清碳酸氢盐水平较低，即使在正常实验室范围内， 与高血压、心血管疾病（CVD）、CKD进展和死亡风险密切相关。动脉 功能障碍在肾脏疾病过程的早期开始，并且是导致肾脏疾病发展的关键因素。 左心室肥厚（LVH）。LVH是心血管死亡率的最强预测因子 在CKD中。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 以促进尿酸排泄。所有这三种体液因素都直接和间接地诱导 内皮功能障碍、血管僵硬、LVH和血管钙化。小型干预性试验 表明用碱疗法治疗减缓了肾脏疾病的进展，即使在正常的患者中也是如此。 血清碳酸氢盐水平。由于CVD和CKD进展的风险因素通常重叠，因此在生物学上是 CKD患者的碱疗法也可能改善心血管结局。在我们 初步数据显示，碱疗法改善了16例CKD 3 - 4期患者的血管内皮功能。 因此，碱疗法可能是CKD的一种廉价且新颖的治疗模式。 我们建议对108例CKD患者进行一项随机、双盲、安慰剂对照、为期12个月的试验 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 假设用碳酸氢盐治疗将改善患者的血管功能和LVH指标 CKD 3 - 4期。我们的主要目标是确定碱疗法改善血管紧张素转换酶活性的有效性。 使用无创性血管造影技术评估CKD 3 - 4期患者的内皮功能和降低大弹性动脉硬度 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介导的扩张随时间的变化。 碳酸氢钠治疗或安慰剂治疗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的LVMI随时间的变化， 碳酸氢钠治疗或安慰剂。在目标3中，我们将比较体液免疫指标随时间的变化， 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）和一种新的钙化测试，提供了一个衡量整体钙化倾向， 碳酸氢钠治疗或安慰剂治疗12个月后的血清T50。这项新研究的结果表明， 通过提供必要证据以确定碳酸氢钠，为临床实践提供信息的可能性 作为治疗患者动脉功能障碍的廉价且易于管理的选择， CKD 3 - 4期。

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.