单位：[1]Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, Suite 2000, New Orleans, LA 70112, USA[2]Department of Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA[3]Department of Epidemiology & Biostatistics, University of Georgia College of Public Health, Athens, GA, USA[4]Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China[5]Metabolon, Inc., Morrisville, NC, USA[6]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA[7]Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA[8]Division of Nephrology, Tufts Medical Center, Boston, MA, USA[9]Department of General Internal Medicine, University of California San Francisco, San Francisco, CA, USA
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 m(2)). 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 m(2)). 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.
基金：
National Institute on Aging of the NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG041200, R21AG051914]; National Institute of General Medical Sciences of the NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P20GM109036]; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P20GM109036] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R21AG051914, R01AG041200] Funding Source: NIH RePORTER
第一作者单位：[1]Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, Suite 2000, New Orleans, LA 70112, USA
通讯作者：
推荐引用方式(GB/T 7714)：
Nierenberg Jovia L.,He Jiang,Li Changwei,et al.Novel associations between blood metabolites and kidney function among Bogalusa Heart Study and Multi-Ethnic Study of Atherosclerosis participants[J].METABOLOMICS.2019,15(12):doi:10.1007/s11306-019-1613-3.
APA：
Nierenberg, Jovia L.,He, Jiang,Li, Changwei,Gu, Xiaoying,Shi, Mengyao...&Kelly, Tanika N..(2019).Novel associations between blood metabolites and kidney function among Bogalusa Heart Study and Multi-Ethnic Study of Atherosclerosis participants.METABOLOMICS,15,(12)
MLA：
Nierenberg, Jovia L.,et al."Novel associations between blood metabolites and kidney function among Bogalusa Heart Study and Multi-Ethnic Study of Atherosclerosis participants".METABOLOMICS 15..12(2019)
