Plasma metabolites mediate the association of total and specific fruit intake with incident chronic kidney disease risk

<i>Background</i>: The relationship between total and specific fruit consumption and chronic kidney disease (CKD) risk remains unclear, and the underlying mechanisms are poorly understood. This study aimed to investigate the association between fruit intake and incident CKD risk and explore the mediating role of metabolic signatures. <i>Methods</i>: We analyzed data of 98 065 CKD-free participants from the UK Biobank with nuclear magnetic resonance metabolomics data. Fruit consumption (total fruit, citrus fruits, berries, apples/pears, dried fruits, stewed fruits, and other fruits) was assessed using a 24-hour dietary questionnaire. Metabolic signatures were identified using LASSO regression. <i>Results</i>: Over a median follow-up of 12.2 years, 2716 participants developed CKD. Higher intake of total fruits (per 1 SD increment: adjusted HR, 0.94; 95% CI, 0.90-0.97), citrus fruits (per 1 SD increment: adjusted HR, 0.92; 95% CI, 0.88-0.96), and berries (per 1 SD increment: adjusted HR, 0.95; 95% CI, 0.91-0.99) was significantly associated with a reduced risk of incident CKD. No significant associations were observed for apples and pears, dried fruits, or stewed fruits. CKD risk-specific metabolic signature scores for total fruits, citrus fruits, and berries were constructed, including the glutamine level, the 3-hydroxybutyrate level, the degree of unsaturation, the ratio of polyunsaturated to monounsaturated fatty acids, and the omega-3 and docosahexaenoic acid percentages. These scores mediated 25.5%, 8.6%, and 15.8% of the associations between total fruit, citrus fruit, and berry consumption and CKD risk, respectively. <i>Conclusions</i>: The protective effects of total fruits, citrus fruits, and berries on CKD risk are partially mediated by metabolic signatures. Monitoring plasma metabolites may enhance precision in dietary recommendations for CKD prevention.