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饮料消费对慢性肾衰竭风险的影响及血清代谢物的中介作用:基于孟德尔随机化研究

The impact of beverage consumption on chronic renal failure risk and the mediation of serum metabolites: based on Mendelian randomization study.

作者信息

Wei Zhengshu, Mo Dunsheng, Lü Wenxin, Wu Shangxin, Zhang Yan, Tang Zhen, Fan Yongyi

机构信息

Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Guangxi, 545005, China.

出版信息

Genes Nutr. 2025 Jul 11;20(1):14. doi: 10.1186/s12263-025-00773-w.

Abstract

BACKGROUND

Chronic renal failure (CRF), the end-stage of chronic kidney disease, affects approximately 10% of the global population. While associations between beverage consumption and renal function have been reported, their causal relationships remain unclear. This study aimed to investigate the causal relationships between different beverage consumption and CRF, as well as the mediating effects of serum metabolites.

METHODS

Using a two-sample Mendelian randomization (MR) approach, we analyzed genetic data from the UK Biobank and GWAS databases. We examined bidirectional causal relationships between water, coffee, tea, and alcohol consumption with CRF, and screened metabolites significantly associated with CRF from 1,400 metabolites for mediation analysis. Additionally, we evaluated the mediating effects of these metabolites in the relationship between beverage consumption and CRF.

RESULTS

MR analysis showed evidence for a causal association between tea consumption and reduced CRF risk (OR = 0.314, 95% CI: 0.155-0.634, p = 0.001), while alcohol consumption was causally associated with increased CRF risk (OR = 1.275, 95% CI: 1.046-1.553, p = 0.016). Water and coffee consumption showed no significant associations with CRF. Further analysis identified 11 metabolites significantly associated with CRF. Salicylate demonstrated a positive mediating effect (12.5%) in the association between tea consumption and CRF risk, while 3-methyl catechol sulfate (-25.70%), glutarate (C5-DC) (-14.60%), and X-23,655 (-18.7%) showed negative mediating effects. In the alcohol consumption-CRF pathway, the ornithine-to-phosphate ratio exhibited a positive mediating effect, while X-23,655 showed a negative mediating effect.

CONCLUSION

This study provides evidence for a potential protective association of tea consumption and a potential harmful association of alcohol consumption with CRF risk, partially mediated through specific serum metabolites. These findings contribute new insights into potential CRF prevention strategies and may inform dietary guidelines.

摘要

背景

慢性肾衰竭(CRF)是慢性肾脏病的终末期,影响着全球约10%的人口。虽然已有关于饮料消费与肾功能之间关联的报道,但其因果关系仍不明确。本研究旨在探讨不同饮料消费与CRF之间的因果关系,以及血清代谢物的中介作用。

方法

采用两样本孟德尔随机化(MR)方法,我们分析了来自英国生物银行和全基因组关联研究(GWAS)数据库的遗传数据。我们研究了水、咖啡、茶和酒精消费与CRF之间的双向因果关系,并从1400种代谢物中筛选出与CRF显著相关的代谢物进行中介分析。此外,我们评估了这些代谢物在饮料消费与CRF关系中的中介作用。

结果

MR分析显示,饮茶与降低CRF风险之间存在因果关联的证据(比值比[OR]=0.314,95%置信区间[CI]:0.155-0.634,p=0.001),而饮酒与CRF风险增加存在因果关联(OR=1.275,95%CI:1.046-1.553,p=0.016)。水和咖啡消费与CRF无显著关联。进一步分析确定了11种与CRF显著相关的代谢物。水杨酸在饮茶与CRF风险的关联中显示出正向中介作用(12.5%),而3-甲基儿茶酚硫酸盐(-25.70%)、戊二酸(C5-DC)(-14.60%)和X-23,655(-18.7%)显示出负向中介作用。在饮酒-CRF途径中,鸟氨酸与磷酸盐的比值显示出正向中介作用,而X-23,655显示出负向中介作用。

结论

本研究为饮茶与CRF风险之间潜在的保护关联以及饮酒与CRF风险之间潜在的有害关联提供了证据,部分通过特定血清代谢物介导。这些发现为潜在的CRF预防策略提供了新见解,并可能为饮食指南提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/12247210/63b25729beca/12263_2025_773_Fig1_HTML.jpg

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