Abstract
Introduction
Chronic kidney disease (CKD) is an important cause of disability and death, but its pathogenesis is poorly understood. Plasma metabolites can provide insights into underlying processes associated with CKD.
Objectives
To clarify the relationship of plasma metabolites with CKD and renal function in human.
Methods
We used a targeted metabolomics approach to characterize the relationship of 450 plasma metabolites with CKD and estimated glomerular filtration rate (eGFR) in 616 adults, aged 38–94 years, who participated in the Baltimore Longitudinal Study of Aging.
Results
There were 74 (12.0%) adults with CKD. Carnitine, acetylcarnitine, propionylcarnitine, butyrylcarnitine, trigonelline, trimethylamine N-oxide (TMAO), 1-methylhistidine, citrulline, homoarginine, homocysteine, sarcosine, symmetric dimethylarginine, aspartate, phenylalanine, taurodeoxycholic acid, 3-indolepropionic acid, phosphatidylcholines (PC).aa.C40:2, PC.aa.C40:3, PC.ae.C40:6, triglycerides (TG) 20:4/36:3, TG 20:4/36:4, and choline were associated with higher odds of CKD in multivariable analyses adjusting for potential confounders and using a false discovery rate (FDR) to address multiple testing. Six acylcarnitines, trigonelline, TMAO, 18 amino acids and biogenic amines, taurodeoxycholic acid, hexoses, cholesteryl esters 22:6, dehydroepiandrosterone sulfate, 3-indolepropionic acid, 2 PCs, 17 TGs, and choline were negatively associated with eGFR, and hippuric acid was positively associated with eGFR in multivariable analyses adjusting for potential confounders and using a FDR approach.
Conclusion
The metabolites associated with CKD and reduced eGFR suggest that several pathways, such as the urea cycle, the arginine-nitric oxide pathway, the polyamine pathway, and short chain acylcarnitine metabolism are altered in adults with CKD and impaired renal function.
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Data availability
Data are available upon reasonable request.
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Funding
This study was supported by the National Institutes of Health R01 AG027012, R01 AG057723, P30 AG021334 Johns Hopkins University Older Americans Independence Center, and the Intramural Research Program of the National Institute on Aging, Baltimore, Maryland.
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RDS and LF designed the study; YY and MZ created the dataset; YY analyzed the data; YY, RDS, MZ, RM, LF, and TKC interpreted the data: YY, RDS, MZ, and RM drafted the manuscript; all authors revised the manuscript; all authors approved the final version.
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Yamaguchi, Y., Zampino, M., Moaddel, R. et al. Plasma metabolites associated with chronic kidney disease and renal function in adults from the Baltimore Longitudinal Study of Aging. Metabolomics 17, 9 (2021). https://doi.org/10.1007/s11306-020-01762-3
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DOI: https://doi.org/10.1007/s11306-020-01762-3