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.