Plasma metabolites associated with chronic kidney disease and renal function in adults from the Baltimore Longitudinal Study of Aging

Yuko Yamaguchi, Marta Zampino, Ruin Moaddel, Teresa K. Chen, Qu Tian, Luigi Ferrucci, Richard D. Semba

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number9
JournalMetabolomics
Volume17
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Aging
  • Biomarker
  • Chronic kidney disease
  • Glomerular filtration rate
  • Mass spectrometry
  • Metabolomics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

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