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: 10681199
• 负责人: Kalani Lukela Raphael
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10681199
• 关键词: Acid-Base Equilibrium; Acidity; Acids; Affect; Alkalies; Ammonia; Ammonium; Animal Model; Bicarbonates; Blood; Bone Density; Cardiovascular Diseases; Catabolism; Chronic Kidney Failure; Clinic; Clinical; Clinical Trials; Cohort Studies; Collagen Type I; Collection; Complement Activation; Consumption; Cross-Sectional Studies; Diabetes Mellitus; Diet; Dietary History; End stage renal failure; Excretory function; Functional disorder; General Population; Hand; Hand Strength; Health; Hip region structure; Home; Hour; Hypertension; Impairment; Inflammation; Injury to Kidney; Intake; Intervention; Intervention Trial; Isometric Exercise; Kidney; Kidney Diseases; LCN2 gene; Linear Regressions; Link; Logistic Regressions; Measurement; Measures; Mediating; Metabolic acidosis; Muscle; Musculoskeletal; N-terminal; Nephrons; Normal Range; Nutritional; Oral; Organ; Outcome; PTH gene; Participant; Pathway interactions; Pharmacology; Physical Function; Physical Performance; Production; Regression Analysis; Renal function; Risk; Sampling; Serum; Signal Transduction; Supplementation; Testing; Transforming Growth Factors; Translating; Type I Procollagen; Urine; Venous; Vertebral column; Veterans; alkalinity; base; bone; bone health; bone preservation; calcium excretion; clinical practice; complement pathway; cost; crosslink; demineralization; design; diabetes control; dietary; disorder prevention; frailty; high risk; hypertension control; improved; kidney fibrosis; kidney preservation; muscle strength; organ injury; pleiotropism; preservation; prevent; quadriceps muscle; rat KIM-1 protein; response; translational impact; urinary; western diet

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.

慢性肾脏病 (CKD) 是一种常见、病态且代价高昂的疾病，对退伍军人有重大影响 健康。除了控制糖尿病和高血压外，没有其他疗法可以预防 CKD。结果 大型队列研究表明，酸性含量较高的饮食会增加患 CKD 和最终疾病的风险 阶段肾病。此外，膳食酸过多和代谢性酸中毒与骨脱矿质有关， 肌肉分解代谢和身体功能障碍也可能影响退伍军人的健康。中的一个 将这些发现转化为临床的挑战在于，膳食酸过量通常是由以下因素决定的： 饮食史，在临床实践中往往不准确且不切实际。还有一个就是最 常用测量的酸碱指标，血清碳酸氢盐，即使在正常情况下也可能处于正常范围内。 设置高酸饮食。这是因为尿铵排泄量随着膳食酸的增加而增加。 促进酸排泄和新碳酸氢盐的形成，最终维持血清碳酸氢盐和 pH值在正常范围内。此外，肾内氨生成增加会导致动物肾纤维化 模型。因此，高尿铵排泄可能是酸介导的器官损伤的信号。 正常血清碳酸氢盐浓度。本研究的假设是尿铵排泄， 直接测量膳食酸负荷，与肾损伤和骨骼受损更相关 肾功能完好的退伍军人的肌肉健康状况高于血清碳酸氢盐浓度。穿过- 建议对 260 名肾功能完好且患有糖尿病或高血压的退伍军人进行分段研究 研究这个假设。参与者将在家中收集 24 小时尿液样本，同时食用平常的食物 饮食。 24 小时尿液收集的尿铵排泄量和静脉碳酸氢盐浓度将 测量。将进行调整后的线性和逻辑回归分析来比较 尿铵和血清碳酸氢盐与肾脏、骨骼和肌肉健康标志物的关联。这 主要肾脏、骨骼和肌肉结果是尿转化生长因子-b1、骨矿物质密度 分别是髋部总力量和股四头肌力量。探索性分析将比较尿的关联 铵和血清碳酸氢盐与尿肾损伤分子-1和中性粒细胞明胶酶相关 脂质运载蛋白水平；腰椎骨矿物质密度、尿钙排泄量和血清交联水平 1型胶原端肽和I型原胶原完整N末端前肽；握力和短 物理性能电池评分；和虚弱。据推测，尿液中存在铵，但血清中不存在。 碳酸氢盐，可识别亚临床肾损伤以及肌肉和骨骼健康受损。如果达到预期的结果 据观察，他们支持尿铵作为识别退伍军人饮食的实用手段 酸介导的器官损伤。研究结果可以加强案例的实施并为大型项目的设计提供信息 临床试验测试营养或药物碱性疗法对预防 CKD 的多效作用 以及保持高膳食酸摄入量的退伍军人的骨骼和肌肉健康。