Acid-base balance and kidney, bone, and muscle health in Veterans with preserved renal function

肾功能完好的退伍军人的酸碱平衡与肾脏、骨骼和肌肉健康

• 批准号: 10402430
• 负责人: Kalani Lukela Raphael
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402430
• 关键词: Acid; base; balance; kidney; bone

Chronic kidney disease (CKD) is a common, morbid, and costly condition that significantly impacts Veteran health. Apart from diabetes and hypertension control, there are no other therapies that prevent CKD. Results from large cohort studies suggest that diets that are higher in acid content increase the risk of CKD and end- stage renal disease. Further, dietary acid excess and metabolic acidosis are linked with bone demineralization, muscle catabolism, and physical dysfunction, which could be impacting Veteran health as well. One of the challenges translating these findings into the clinic is that dietary acid excess is typically determined from dietary histories, which are often inaccurate and impractical in clinical practice. Another is that the most commonly measured acid-base indicator, serum bicarbonate, is likely to be in the normal range even in the setting of a high acid diet. This is because urinary ammonium excretion increases in response to dietary acid to facilitate acid excretion and formation of new bicarbonate, which ultimately maintains serum bicarbonate and pH in the normal range. Further, enhanced intrarenal ammonia production causes kidney fibrosis in animal models. Thus, high urinary ammonium excretion might signal acid-mediated organ injury in the setting of a normal serum bicarbonate concentration. The hypothesis of this study is that urinary ammonium excretion, as a direct measurement of dietary acid load, is better associated with kidney injury and impaired bone and muscle health in Veterans with preserved kidney function than serum bicarbonate concentration. A cross- sectional study of 260 Veterans with preserved kidney function and diabetes or hypertension is proposed to investigate this hypothesis. Participants will collect 24-hour urine samples at home while consuming their usual diet. Urinary ammonium excretion from 24-hour urine collections and venous bicarbonate concentration will be measured. Adjusted linear and logistic regression analyses will be performed to compare the strength of the associations of urinary ammonium and serum bicarbonate with kidney, bone, and muscle health markers. The primary kidney, bone, and muscle outcomes are urinary transforming growth factor-b1, bone mineral density at the total hip, and quadriceps strength, respectively. Exploratory analyses will compare associations of urinary ammonium and serum bicarbonate with urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin levels; lumbar spine bone mineral density, urinary calcium excretion, and serum levels of cross-linked telopeptide of type 1 collagen and procollagen type I intact N-terminal propeptide; hand-grip strength and Short Physical Performance Battery score; and frailty. It is hypothesized that urinary ammonium, but not serum bicarbonate, identifies subclinical kidney injury and impaired muscle and bone health. If the expected results are observed, they would support urinary ammonium as a practical means of identifying Veterans with dietary acid-mediated organ injury. The results could strengthen the case to conduct and inform the design of a large clinical trial testing pleiotropic effects of nutritional or pharmacological alkaline therapies on CKD prevention and preservation of bone and muscle health in Veterans with high dietary acid intake.

慢性肾脏疾病（CKD）是一种常见，病态且昂贵的状况，对退伍军人产生重大影响 健康。除了糖尿病和高血压控制外，没有其他疗法可以阻止CKD。结果 来自大型队列研究表明，酸含量较高的饮食会增加CKD和最终的风险 阶段肾脏疾病。此外，饮食中的酸过量和代谢性酸中毒与骨脱矿化有关， 肌肉分解代谢和身体功能障碍，这也可能影响退伍军人健康。中的一个 将这些发现转化为诊所的挑战是，饮食中的饮食中过量通常是由 饮食历史，在临床实践中通常不准确且不切实际。另一个是最多 通常测量的酸碱指示剂血清碳酸氢盐，即使在 设置高酸饮食。这是因为尿铵排泄量因饮食酸而增加 促进酸排泄和新碳酸氢盐的形成，最终保持血清碳酸氢盐和 pH在正常范围内。此外，增强的培育氨产生会导致动物的肾纤维化 型号。因此，高尿铵排泄可能在A的情况下向酸介导的器官损伤表示 正常血清碳酸氢盐浓度。这项研究的假设是尿铵排泄，如 直接测量饮食酸负荷，与肾损伤和骨骼受损更好地相关 与血清碳酸氢盐浓度相比，保留肾功能的退伍军人的肌肉健康。穿过- 对260名保留肾脏功能和糖尿病或高血压的退伍军人进行的分段研究。 研究这一假设。参与者将在家里收集24小时的尿液样本，同时消费他们通常 饮食。来自24小时尿液收集和静脉碳酸氢盐浓度的尿铵排泄物将是 测量。将进行调整的线性和逻辑回归分析，以比较 尿铵和血清碳酸氢盐与肾脏，骨骼和肌肉健康标记的关联。这 一肾，骨和肌肉结局是尿转化生长因子-B1，骨矿物质密度 总臀部和股四头肌强度。探索性分析将比较尿液的关联 氨和血清碳酸氢苯甲酸盐和尿肾损伤分子1和中性粒细胞明胶酶相关 Lipocalin水平；腰椎骨矿物质密度，尿钙排泄和交联血清水平 1型胶原蛋白和procollagen I型完整的N末端丙肽的端肽；手握力和短 身体性能电池得分；和脆弱。假设尿铵，而不是血清 碳酸氢盐，确定亚临床肾脏损伤，肌肉和骨骼健康受损。如果预期结果 观察到，它们将支持尿铵作为确定饮食中退伍军人的一种实用手段 酸介导的器官损伤。结果可以加强案件，以进行大型的设计和告知设计 营养或药理碱性疗法对CKD预防的临床试验测试多效性影响 以及饮食酸摄入量高的退伍军人的骨骼和肌肉健康。