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

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.

SUBMITTER: Nierenberg JL

PROVIDER: S-EPMC7021455 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Nierenberg Jovia L JL He Jiang J Li Changwei C Gu Xiaoying X Shi Mengyao M Razavi Alexander C AC Mi Xuenan X Li Shengxu S Bazzano Lydia A LA Anderson Amanda H AH He Hua H Chen Wei W Kinchen Jason M JM Rebholz Casey M CM Coresh Josef J Levey Andrew S AS Inker Lesley A LA Shlipak Michael M Kelly Tanika N TN

Metabolomics : Official journal of the Metabolomic Society 20191113 12

<h4>Introduction</h4>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.<h4>Objectives</h4>The objective of this study was to elucidate novel metaboli ...[more]

PMID: 31720858

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Project description:Background and aimsDyslipidemia has been identified as a major risk factor for cardiovascular disease. We aimed to identify metabolites and metabolite modules showing novel association with lipids among Bogalusa Heart Study (BHS) participants using untargeted metabolomics.Methods and resultsUntargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to quantify serum metabolites of 1 243 BHS participants (816 whites and 427 African-Americans). The association of single metabolites with lipids was assessed using multiple linear regression models to adjust for covariables. Weighted correlation network analysis was utilized to identify modules of co-abundant metabolites and examine their covariable adjusted correlations with lipids. All analyses were conducted according to race and using Bonferroni-corrected α-thresholds to determine statistical significance. Thirteen metabolites with known biochemical identities showing novel association achieved Bonferroni-significance, p < 1.04 × 10-5, and showed consistent effect directions in both whites and African-Americans. Twelve were from lipid sub-pathways including fatty acid metabolism (arachidonoylcholine, dihomo-linolenoyl-choline, docosahexaenoylcholine, linoleoylcholine, oleoylcholine, palmitoylcholine, and stearoylcholine), monohydroxy fatty acids (2-hydroxybehenate, 2-hydroxypalmitate, and 2-hydroxystearate), and lysoplasmalogens [1-(1-enyl-oleoyl)-GPE (P-18:1) and 1-(1-enyl-stearoyl)-GPE (P-18:0)]. The gamma-glutamylglutamine, peptide from the gamma-glutamyl amino acid sub-pathway, were also identified. In addition, four metabolite modules achieved Bonferroni-significance, p < 1.39 × 10-3, in both whites and African-Americans. These four modules were largely comprised of metabolites from lipid sub-pathways, with one module comprised of metabolites which were not identified in the single metabolite analyses.ConclusionThe current study identified 13 metabolites and 4 metabolite modules showing novel association with lipids, providing new insights into the physiological mechanisms regulating lipid levels.

Project description:PurposeTo quantitatively determine the population variation and relationship of left ventricular (LV) trabeculation to LV function, structure, and clinical variables.Materials and methodsThis HIPAA-compliant multicenter study was approved by institutional review boards of participating centers. All participants provided written informed consent. Participants from the Multi-Ethnic Study of Atherosclerosis with cardiac magnetic resonance (MR) data were evaluated to quantify LV trabeculation as a fractal dimension (FD). Entire cohort participants free of cardiac disease, hypertrophy, hypertension, and diabetes were stratified by body mass index (BMI) into three reference groups (BMI <25 kg/m(2); BMI ≥25 kg/m(2) to <30 kg/m(2); and BMI ≥30 kg/m(2)) to explore maximal apical FD (FDMaxApical). Multivariable linear regression models determined the relationship between FD and other parameters.ResultsIncluded were 2547 participants (mean age, 68.7 years ± 9.1 [standard deviation]; 1211 men). FDMaxApical are in arbitrary units. FDMaxApical reference ranges for BMI 30 kg/m(2) or greater (n = 163), 25 kg/m(2) or greater to less than 30 kg/m(2) (n = 206), and less than 25 kg/m(2) (n = 235) were 1.203 ± 0.06 (95% confidence interval: 1.194, 1.212), 1.194 ± 0.06 (95% confidence interval: 1.186, 1.202), and 1.169 ± 0.05 (95% confidence interval: 1.162, 1.176), respectively. In the entire cohort, adjusted for anthropometrics, trabeculation was higher in African American participants (standardized β [sβ] = 0.09; P ≤ .001) and Hispanic participants (sβ = 0.05; P = .013) compared with white participants and was also higher in African American participants compared with Chinese American participants (sβ = 0.08; P = .01), and this persisted after adjustment for hypertension and LV size. Hypertension (sβ = 0.07; P < .001), LV mass (sβ = 0.22; P < .001), and wall thickness (sβ = 0.27; P < .001) were positively associated with FDMaxApical even after adjustment. In the group with BMIs less than 25 kg/m(2), Chinese American participants had less trabeculation than white participants (sβ = -0.15; P = .032).ConclusionFractal analysis of cardiac MR imaging data measures endocardial complexity, which helps to differentiate normal from abnormal trabecular patterns in healthy versus diseased hearts. Trabeculation is influenced by race and/or ethnicity and, more importantly, by cardiac loading conditions and comorbidities. Clinicians who interpret cine MR imaging data should expect slightly less endocardial complexity in Chinese American patients and more in African American patients, Hispanic patients, hypertensive patients, and those with hypertrophy.

Project description:Previous studies demonstrate associations of low 25-hydroxyvitamin D (25(OH)D) concentrations with low bone mineral density (BMD) and fractures, motivating widespread use of vitamin D supplements for bone health. However, previous studies have been limited to predominantly White populations despite differences in the distribution and metabolism of 25(OH)D by race/ethnicity. We determined associations of serum 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH2)D3), and parathyroid hormone (PTH) with BMD among 1773 adult participants in the Multi-Ethnic Study of Atherosclerosis (MESA) in a staggered cross-sectional study design. Vitamin D metabolites were measured using liquid chromatography-mass spectroscopy and PTH using a 2-site immunoassay from serum collected in 2000-2002. Volumetric trabecular lumbar BMD was measured from computed tomography scans performed in 2002-2005 expressed as g/cm(3). We used linear regression and graphical methods to compare associations of vitamin D metabolite and PTH concentrations with BMD as the outcomes measure among White (n=714), Black (n=353), Chinese (n=249), and Hispanic (n=457) participants. Serum 25(OH)D and 24,25(OH2)D3 concentrations were highest among Whites and lowest among Blacks. BMD was greatest among Black participants. Higher serum 25(OH)D was only associated with higher BMD among Whites and Chinese participants (P-for-interaction=0.054). Comparing the lowest category of 25(OH)D (<20 ng/ml) to the highest (?30 ng/ml), the adjusted mean difference in BMD was -8.1g/cm3 (95% CI -14.8, -1.4) for Whites; -10.2g/cm3 (-20.4, 0.0) for Chinese vs. 8.8 g/cm3 (-2.8, 20.5) for Black and -1.1g/cm3 (-8.3, 6.2) for Hispanic. Similar results were observed for serum 24,25(OH2)D3. Serum PTH was not associated with BMD. In a multi-ethnic population, associations of 25(OH)D with BMD were strongest among White and Chinese participants and null among Black and Hispanic participants. Further studies are needed to determine optimal biomarkers for bone health for multiple ethnic groups.

Dataset Information

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

Publications

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

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