Greater adherence to plant-based diets is associated with a lower risk of incident chronic kidney disease (CKD). Metabolomics can help identify blood biomarkers of plant-based diets and enhance understanding of underlying mechanisms.
Using untargeted metabolomics, we aimed to identify metabolites associated with 4 plant-based diet indices (PDI) [overall PDI, provegetarian diet, healthful PDI, and unhealthful PDI] and incident CKD in 2 subgroups within the Atherosclerosis Risk in Communities Study.
We calculated 4 PDIs based on participants’ responses on a food frequency questionnaire. We used multivariable linear regression to examine the association between 4 PDIs and 374 individual metabolites, adjusting for confounders. We used Cox proportional hazards regression to evaluate associations between PDI-related metabolites and incident CKD. Estimates were meta-analyzed across 2 subgroups (n1=1,762; n2=1,960). We calculated C-statistics to assess whether metabolites improved the prediction of those in the highest quintile vs. lower 4 quintiles of PDIs, and whether PDI- and CKD-related metabolites predicted incident CKD beyond the CKD prediction model.
We identified 82 significant PDI-metabolite associations (overall PDI=27; provegetarian=17; healthful PDI=20; unhealthful PDI=18); 11 metabolites overlapped across the overall PDI, provegetarian diet, and healthful PDI. Addition of metabolites improved prediction of those in the highest quintile vs. lower 4 quintiles of PDIs compared to participant characteristics alone (range of differences in C-statistics=0.026, 0.104; P-value ≤0.001 for all tests). Six PDI-related metabolites (glycerate, 1,5-anhydroglucitol, gamma-glutamylalanine, gamma-glutamylglutamate, gamma-glutamylleucine, gamma-glutamylvaline), involved in glycolysis, gluconeogenesis, and pyruvate metabolism and gamma-glutamyl peptide metabolism, were significantly associated with incident CKD and improved prediction of incident CKD beyond the CKD prediction model (difference in C-statistics for 6 metabolites=0.005, P-value=0.006).
In a community-based study of US adults, we identified metabolites that were related to plant-based diets that predicted incident CKD. These metabolites highlight pathways through which plant-based diets are associated with incident CKD.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.