Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Clin J Am Soc Nephrol. 2023 Mar 1;18(3):327-336. doi: 10.2215/CJN.0000000000000062. Epub 2023 Jan 13.
High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can provide objective biomarkers of ultra-processed food and provide important insights into the mechanisms by which ultra-processed food is associated with risk of incident CKD. Our objective was to identify serum metabolites associated with ultra-processed food consumption and investigate whether ultra-processed food-associated metabolites are prospectively associated with incident CKD.
We used data from 3751 Black and White men and women (aged 45-64 years) in the Atherosclerosis Risk in Communities study. Dietary intake was assessed using a semiquantitative 66-item food frequency questionnaire, and ultra-processed food was classified using the NOVA classification system. Multivariable linear regression models were used to identify the association between 359 metabolites and ultra-processed food consumption. Cox proportional hazards models were used to investigate the prospective association of ultra-processed food-associated metabolites with incident CKD.
Twelve metabolites (saccharine, homostachydrine, stachydrine, N2, N2-dimethylguanosine, catechol sulfate, caffeine, 3-methyl-2-oxovalerate, theobromine, docosahexaenoate, glucose, mannose, and bradykinin) were significantly associated with ultra-processed food consumption after controlling for false discovery rate <0.05 and adjusting for sociodemographic factors, health behaviors, eGFR, and total energy intake. The 12 ultra-processed food-related metabolites significantly improved the prediction of ultra-processed food consumption (difference in C statistics: 0.069, P <1×10 -16 ). Higher levels of mannose, glucose, and N2, N2-dimethylguanosine were associated with higher risk of incident CKD after a median follow-up of 23 years.
We identified 12 serum metabolites associated with ultra-processed food consumption and three of them were positively associated with incident CKD. Mannose and N2, N2-dimethylguanosine are novel markers of CKD that may explain observed associations between ultra-processed food and CKD.
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高超加工食品的消费与 CKD 风险增加有关。然而,目前还没有超加工食品的生物标志物,超加工食品与 CKD 相关的机制也不清楚。代谢组学可以提供超加工食品的客观生物标志物,并为超加工食品与 CKD 风险增加之间的关系提供重要的见解。我们的目的是确定与超加工食品消费相关的血清代谢物,并研究超加工食品相关代谢物是否与 CKD 的发生有前瞻性关联。
我们使用了来自 Atherosclerosis Risk in Communities 研究的 3751 名黑人和白人男性和女性(年龄 45-64 岁)的数据。膳食摄入量通过半定量的 66 项食物频率问卷进行评估,超加工食品采用 NOVA 分类系统进行分类。多变量线性回归模型用于确定 359 种代谢物与超加工食品消费之间的关联。Cox 比例风险模型用于研究超加工食品相关代谢物与 CKD 发生的前瞻性关联。
在控制假发现率<0.05并调整社会人口因素、健康行为、eGFR 和总能量摄入后,有 12 种代谢物(糖精、同型斯德丁、斯德丁、N2、N2-二甲基鸟苷、儿茶素硫酸盐、咖啡因、3-甲基-2-氧代戊酸、可可碱、二十二碳六烯酸、葡萄糖、甘露糖和缓激肽)与超加工食品消费显著相关。这 12 种与超加工食品相关的代谢物显著提高了超加工食品消费的预测能力(差异的 C 统计量:0.069,P<1×10-16)。在中位随访 23 年后,更高水平的甘露糖、葡萄糖和 N2、N2-二甲基鸟苷与 CKD 发生的风险增加相关。
我们确定了 12 种与超加工食品消费相关的血清代谢物,其中 3 种与 CKD 的发生呈正相关。甘露糖和 N2、N2-二甲基鸟苷是 CKD 的新标志物,可能解释了超加工食品与 CKD 之间的观察到的关联。