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.