Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Division of Nephrology, Tufts Medical Center, Boston, MA.
J Nutr. 2019 Apr 1;149(4):578-585. doi: 10.1093/jn/nxy311.
Dietary acid load is a clinically important aspect of the diet that reflects the balance between acid-producing foods, for example, meat and cheese, and base-producing foods, for example, fruits and vegetables.
We used metabolomics to identify blood biomarkers of dietary acid load in 2 independent studies of chronic kidney disease patients: the African American Study of Kidney Disease and Hypertension (AASK, n = 689) and the Modification of Diet in Renal Disease (MDRD, n = 356) study. Multivariable linear regression was used to assess the cross-sectional association between serum metabolites whose identity was known (outcome) and dietary acid load (exposure), estimated with net endogenous acid production (NEAP) based on 24-h urine urea nitrogen and potassium, and adjusted for age, sex, race, randomization group, measured glomerular filtration rate, log-transformed urine protein-to-creatinine ratio, history of cardiovascular disease, BMI, and smoking status.
Out of the 757 known, nondrug metabolites identified in AASK, 26 were significantly associated with NEAP at the Bonferroni threshold for significance (P < 6.6 × 10-5). Twenty-three of the 26 metabolites were also identified in the MDRD study, and 13 of the 23 (57%) were significantly associated with NEAP (P < 2.2 × 10-3), including 5 amino acids (S-methylmethionine, indolepropionylglycine, indolepropionate, N-methylproline, N-δ-acetylornithine), 2 cofactors and vitamins (threonate, oxalate), 1 lipid (chiro-inositol), and 5 xenobiotics (methyl glucopyranoside, stachydrine, catechol sulfate, hippurate, and tartronate). Higher levels of all 13 replicated metabolites were associated with lower NEAP in both AASK and the MDRD study.
Metabolomic profiling of serum specimens from kidney disease patients in 2 study populations identified 13 replicated metabolites associated with dietary acid load. Additional studies are needed to validate these compounds in healthy populations. These 13 compounds may potentially be used as objective markers of dietary acid load in future nutrition research studies.
饮食酸负荷是饮食中一个重要的临床方面，反映了产酸食物（如肉和奶酪）与产碱食物（如水果和蔬菜）之间的平衡。
我们使用代谢组学方法在两项慢性肾脏病患者的独立研究中鉴定饮食酸负荷的血液生物标志物：非裔美国人肾脏病和高血压研究（AASK，n=689）和肾脏疾病饮食改良研究（MDRD，n=356）。多变量线性回归用于评估血清代谢物与其身份已知的（结果）与饮食酸负荷（暴露）之间的横断面关联，根据 24 小时尿尿素氮和钾，基于净内源性酸生成（NEAP）进行估计，并调整年龄、性别、种族、随机分组、测量肾小球滤过率、尿蛋白/肌酐比的对数转换、心血管疾病史、BMI 和吸烟状况。
在 AASK 中鉴定出的 757 种已知非药物代谢物中，有 26 种在显著水平（P < 6.6×10-5）与 NEAP 显著相关。26 种代谢物中有 23 种也在 MDRD 研究中被鉴定出来，其中 13 种（57%）与 NEAP 显著相关（P < 2.2×10-3），包括 5 种氨基酸（S-甲基甲硫氨酸、吲哚丙酸甘氨酸、吲哚丙酸、N-甲基脯氨酸、N-δ-乙酰鸟氨酸）、2 种辅因子和维生素（苏氨酸、草酸盐）、1 种脂质（手性肌醇）和 5 种外源性物质（甲基吡喃葡萄糖苷、莨菪亭、儿茶酚硫酸盐、马尿酸和酒石酸盐）。在 AASK 和 MDRD 研究中，所有 13 种复制代谢物的水平升高都与 NEAP 降低相关。
对来自两个研究人群的肾脏病患者的血清标本进行代谢组学分析，鉴定出 13 种与饮食酸负荷相关的复制代谢物。需要进一步的研究来验证这些化合物在健康人群中的作用。这些 13 种化合物可能在未来的营养研究中作为饮食酸负荷的客观标志物。
