Novel associations between blood metabolites and kidney function among Bogalusa Heart Study and Multi-Ethnic Study of Atherosclerosis participants

Jovia L. Nierenberg, Jiang He, Changwei Li, Xiaoying Gu, Mengyao Shi, Alexander C. Razavi, Xuenan Mi, Shengxu Li, Lydia A. Bazzano, Amanda H. Anderson, Hua He, Wei Chen, Jason M. Kinchen, Casey M. Rebholz, Josef Coresh, Andrew S. Levey, Lesley A. Inker, Michael Shlipak, Tanika N. Kelly

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Introduction: Chronic kidney disease (CKD) is a major public health challenge given its high global prevalence and associated risks of cardiovascular disease and progression to end stage renal disease. Although it is known that numerous metabolic changes occur in CKD patients, identifying novel metabolite associations with kidney function may enhance our understanding of the physiologic pathways relating to CKD. Objectives: The objective of this study was to elucidate novel metabolite associations with kidney function among participants of two community-based cohorts with carefully ascertained metabolomics, kidney function, and covariate data. Methods: Untargeted ultrahigh-performance liquid chromatography–tandem mass spectrometry was used to detect and quantify blood metabolites. We used multivariate adjusted linear regression to examine associations between single metabolites and creatinine-based estimated glomerular filtration rate (eGFRcr) among 1243 Bogalusa Heart Study (BHS) participants (median eGFRcr: 94.4, 5th–95th percentile: 66.0–119.6 mL/min/1.73 m2). Replication, determined by statistical significance and consistent effect direction, was tested using gold standard measured glomerular filtration rate (mGFR) among 260 Multi-Ethnic Study of Atherosclerosis (MESA) participants (median mGFR: 72.0, 5th–95th percentile: 43.5–105.0 mL/min/1.73 m2). All analyses used Bonferroni-corrected alpha thresholds. Results: Fifty-one novel metabolite associations with kidney function were identified, including 12 from previously unrelated sub-pathways: N6-carboxymethyllysine, gulonate, quinolinate, gamma-CEHC-glucuronide, retinol, methylmalonate, 3-hydroxy-3-methylglutarate, 3-aminoisobutyrate, N-methylpipecolate, hydroquinone sulfate, and glycine conjugates of C10H12O2 and C10H14O2(1). Significant metabolites were generally inversely associated with kidney function and smaller in mass-to-charge ratio than non-significant metabolites. Conclusion: The 51 novel metabolites identified may serve as early, clinically relevant, kidney function biomarkers.

Original languageEnglish (US)
Article number149
JournalMetabolomics
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2019

Keywords

  • Glomerular filtration rate
  • Kidney
  • Kidney disease
  • Metabolome
  • Metabolomics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

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