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

慢性肾脏疾病(CKD)是一种常见的、病态的和昂贵的疾病，对退伍军人的影响很大 健康。除了控制糖尿病和高血压，没有其他疗法可以预防CKD。结果 来自大型队列研究表明，酸含量较高的饮食会增加慢性肾脏病的风险，并导致 肾脏疾病的阶段。此外，饮食中过量的酸和代谢性酸中毒与骨骼脱矿有关， 肌肉分解代谢和身体功能障碍，这也可能影响退伍军人的健康。其中一个 将这些发现转化为临床面临的挑战是，饮食中的酸过量通常是由 饮食历史，这在临床实践中往往是不准确和不切实际的。另一个是最多的 通常测量的酸碱指标，血清碳酸氢盐，可能在正常范围内，即使在 设置高酸度饮食。这是因为尿铵排泄量增加是对饮食酸度的反应 促进酸排泄和形成新的碳酸氢盐，最终维持血清碳酸氢盐和 PH值在正常范围内。此外，肾内氨产生增加会导致动物肾脏纤维化。 模特们。因此，高尿铵排泄可能是酸介导的器官损伤的信号。 正常的血清碳酸氢盐浓度。这项研究的假设是尿铵排泄，如 直接测量饮食中的酸负荷，与肾脏损伤和骨骼受损有更好的相关性 保留肾功能的退伍军人肌肉健康程度高于血清碳酸氢盐浓度。一个十字- 建议对260名肾功能正常且患有糖尿病或高血压的退伍军人进行横断面研究 研究这一假设。参与者将在家中采集24小时尿样，同时饮用他们平时 节食。24小时尿液收集的尿铵排泄量和静脉碳酸氢盐浓度将 量过了。将进行调整的线性和Logistic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物的关系。这个 肾脏、骨骼和肌肉的主要结果是尿转化生长因子-b1，骨密度 分别是髋关节总力量和股四头肌力量。探索性分析将比较尿液的相关性 尿液中肾损伤分子-1和中性粒细胞明胶酶相关的碳酸氢盐和血清碳酸氢盐 Lipocalin水平；腰椎骨密度、尿钙排泄和血清交联物水平 I型胶原端肽和I型前胶原完整N端肽；握力和握力短 身体性能电池得分；和脆弱。推测是尿氨，而不是血清 碳酸氢盐，识别亚临床肾脏损伤和受损的肌肉和骨骼健康。如果预期的结果 被观察到，他们将支持尿铵作为识别退伍军人饮食的实用手段 酸引起的器官损伤。研究结果可以加强案例的指导和指导，为大型 营养或药理碱疗法预防慢性肾脏病多效作用的临床试验 以及保持退伍军人的骨骼和肌肉健康与高膳食酸摄入量。

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.