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、昂贵的疾病，严重影响着退伍军人

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.