TY - JOUR
T1 - Novel associations between blood metabolites and kidney function among Bogalusa Heart Study and Multi-Ethnic Study of Atherosclerosis participants
AU - Nierenberg, Jovia L.
AU - He, Jiang
AU - Li, Changwei
AU - Gu, Xiaoying
AU - Shi, Mengyao
AU - Razavi, Alexander C.
AU - Mi, Xuenan
AU - Li, Shengxu
AU - Bazzano, Lydia A.
AU - Anderson, Amanda H.
AU - He, Hua
AU - Chen, Wei
AU - Kinchen, Jason M.
AU - Rebholz, Casey M.
AU - Coresh, Josef
AU - Levey, Andrew S.
AU - Inker, Lesley A.
AU - Shlipak, Michael
AU - Kelly, Tanika N.
N1 - Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - Glomerular filtration rate
KW - Kidney
KW - Kidney disease
KW - Metabolome
KW - Metabolomics
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U2 - 10.1007/s11306-019-1613-3
DO - 10.1007/s11306-019-1613-3
M3 - Article
C2 - 31720858
AN - SCOPUS:85074933858
SN - 1573-3882
VL - 15
JO - Metabolomics
JF - Metabolomics
IS - 12
M1 - 149
ER -