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）是一种常见的，病态的，昂贵的条件，显着影响退伍军人 健康除了糖尿病和高血压控制，没有其他治疗方法可以预防CKD。结果 来自大型队列研究的研究表明，酸含量较高的饮食会增加CKD的风险， 肾病分期此外，膳食酸过量和代谢性酸中毒与骨脱矿有关， 肌肉痉挛和身体功能障碍，这也可能影响退伍军人的健康。之一 将这些发现转化为临床的挑战是，膳食酸过量通常由以下因素确定： 饮食史，这在临床实践中往往是不准确和不切实际的。另一个是， 通常测量的酸碱指标，血清碳酸氢盐，即使在正常范围内， 高酸饮食的设置。这是因为尿铵排泄增加，以响应膳食酸， 促进酸排泄和形成新的碳酸氢盐，最终维持血清碳酸氢盐， pH值在正常范围内。此外，增强的肾内氨产生导致动物肾纤维化。 模型因此，高尿铵排泄可能标志着酸介导的器官损伤， 血清碳酸氢盐浓度正常。这项研究的假设是，尿铵排泄，作为 饮食酸负荷的直接测量，与肾损伤和骨损伤有更好的相关性， 肌肉健康与保留肾功能的退伍军人比血清碳酸氢盐浓度。十字架- 对260名肾功能保留的退伍军人和糖尿病或高血压患者进行了横断面研究， 调查这个假设。参与者将在家中收集24小时尿液样本， 饮食.将从24小时尿液采集的尿铵排泄量和静脉碳酸氢盐浓度 测定了将进行调整后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、骨骼和肌肉健康标志物的相关性。的 主要的肾脏、骨骼和肌肉结果是尿转化生长因子-b1， 全髋关节和股四头肌力量。探索性分析将比较尿液中 尿肾损伤分子-1和中性粒细胞明胶酶相关蛋白 脂质运载蛋白水平;腰椎骨密度、尿钙排泄和血清交联 1型胶原的端肽和I型前胶原的完整N-末端前肽;握力和Short 体能成套测验评分;和虚弱。据推测，尿铵，而不是血清 碳酸氢盐，识别亚临床肾损伤和受损的肌肉和骨骼健康。如果预期的结果 观察到，他们将支持尿铵作为识别饮食失调的退伍军人的一种实用手段。 酸介导的器官损伤研究结果可加强案例指导，并为大型设计提供参考 测试营养或药物碱性疗法对CKD预防的多效性作用的临床试验 以及保持高膳食酸摄入量的退伍军人的骨骼和肌肉健康。