Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study

• Published in: Kidney medicine Vol. 6; no. 4; p. 100793
• Main Authors: Bernard, Lauren, Chen, Jingsha, Kim, Hyunju, Wong, Kari E., Steffen, Lyn M., Yu, Bing, Boerwinkle, Eric, Levey, Andrew S., Grams, Morgan E., Rhee, Eugene P., Rebholz, Casey M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2024; Elsevier
• Subjects: Chronic kidney disease; dietary protein; metabolomics; protein sources; Chronic kidney disease; dietary protein; metabolomics; protein sources
• ISSN: 2590-0595; 2590-0595
• DOI: 10.1016/j.xkme.2024.100793

While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein–related metabolites are associated with incident chronic kidney disease (CKD). Prospective cohort study. A total of 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline. Dietary intake of 6 protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry), serum metabolites. Incident CKD (estimated glomerular filtration rate<60mL/min/1.73m2 with≥25% estimated glomerular filtration rate decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease). Multivariable linear regression models estimated cross-sectional associations between protein-rich foods and serum metabolites. C statistics assessed the ability of the metabolites to improve the discrimination of highest versus lower 3 quartiles of intake of protein-rich foods beyond covariates (demographics, clinical factors, health behaviors, and the intake of nonprotein food groups). Cox regression models identified prospective associations between protein-related metabolites and incident CKD. Thirty significant associations were identified between protein-rich foods and serum metabolites (fish, n=8; nuts, n=5; legumes, n=0; red and processed meat, n=5; eggs, n=3; and poultry, n=9). Metabolites collectively and significantly improved the discrimination of high intake of protein-rich foods compared with covariates alone (difference in C statistics=0.033, 0.051, 0.003, 0.024, and 0.025 for fish, nuts, red and processed meat, eggs, and poultry-related metabolites, respectively; P<1.00 ×10-16 for all). Dietary intake of fish was positively associated with 1-docosahexaenoylglycerophosphocholine (22:6n3), which was inversely associated with incident CKD (HR, 0.82; 95% CI, 0.75-0.89; P=7.81 ×10-6). Residual confounding and sample-storage duration. We identified candidate biomarkers of fish, nuts, red and processed meat, eggs, and poultry. A fish-related metabolite, 1-docosahexaenoylglycerophosphocholine (22:6n3), was associated with a lower risk of CKD. In this study, we aimed to identify associations between protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry) and serum metabolites, which are small biological molecules involved in metabolism. Metabolites significantly associated with a protein-rich food individually and collectively improved the discrimination of the respective protein-rich food, suggesting that these metabolites should be prioritized in future diet biomarker research. We also studied associations between significant diet-related metabolites and incident kidney disease. One fish-related metabolite was associated with a lower kidney disease risk. This finding supports the recent nutritional guidelines recommending a Mediterranean diet, which includes fish as the main dietary protein source.