Bicarbonate Administration In CKD

项目摘要/摘要 胃酸滞留是慢性肾脏疾病(CKD)的常见并发症，因为患病的肾脏无法 排泄每日饮食中的酸负荷。较低的血清碳酸氢盐水平，即使在正常的实验室范围内， 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 功能障碍开始于肾脏疾病的早期，是导致 这一人群中的左心室肥厚(LVH)。左心室肥厚是心血管死亡率的最强预测因子 在CKD中。酸滞留导致血管紧张素II、内皮素-1和醛固酮依次增加 以增加尿酸排泄。这三种体液因素都直接或间接地导致了 内皮功能障碍、血管僵硬、左心室肥厚和血管钙化。小型干预性试验 研究表明，碱疗法可以减缓肾脏疾病的进展，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进展的风险因素经常重叠，因此从生物学角度来说 CKD患者的碱疗可能也会改善心血管预后。在我们的 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，碱疗法可能是治疗慢性肾脏病的一种廉价而新颖的治疗模式。 我们建议对108名慢性肾脏病患者进行为期12个月的随机、双盲、安慰剂对照试验。 阶段3-4检查碳酸氢钠治疗对心血管疾病替代措施的影响。我们的整体 假设碳酸氢盐治疗将改善患者的血管功能和左心室肥厚指标 慢性肾脏病3-4期。我们的主要目标是确定碱疗法改善血管的疗效。 无创性治疗CKD 3-4期患者的内皮功能和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岁后左心室重量指数随时间的变化，由无Gd心脏磁共振成像测量 几个月的碳酸氢钠治疗或安慰剂。在目标3中，我们将比较幽默随着时间的变化 促进血管钙化的尿酸排泄介质(血管紧张素II、内皮素-1和 和一种新的钙化测试，该测试提供了一种测量整体钙化倾向的方法 碳酸氢钠治疗或安慰剂治疗12个月后血清(T50)。这项新颖的研究结果具有 通过提供必要的证据来确定碳酸氢钠的临床实践的可能性 作为治疗动脉功能不全患者的一种廉价且易于管理的选择 慢性肾脏病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.