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The Serum Metabolome Identifies Biomarkers of Dietary Acid Load in 2 Studies of Adults with Chronic Kidney Disease.

ABSTRACT: BACKGROUND:Dietary acid load is a clinically important aspect of the diet that reflects the balance between acid-producing foods, for example, meat and cheese, and base-producing foods, for example, fruits and vegetables. METHODS:We used metabolomics to identify blood biomarkers of dietary acid load in 2 independent studies of chronic kidney disease patients: the African American Study of Kidney Disease and Hypertension (AASK, n = 689) and the Modification of Diet in Renal Disease (MDRD, n = 356) study. Multivariable linear regression was used to assess the cross-sectional association between serum metabolites whose identity was known (outcome) and dietary acid load (exposure), estimated with net endogenous acid production (NEAP) based on 24-h urine urea nitrogen and potassium, and adjusted for age, sex, race, randomization group, measured glomerular filtration rate, log-transformed urine protein-to-creatinine ratio, history of cardiovascular disease, BMI, and smoking status. RESULTS:Out of the 757 known, nondrug metabolites identified in AASK, 26 were significantly associated with NEAP at the Bonferroni threshold for significance (P < 6.6 × 10-5). Twenty-three of the 26 metabolites were also identified in the MDRD study, and 13 of the 23 (57%) were significantly associated with NEAP (P < 2.2 × 10-3), including 5 amino acids (S-methylmethionine, indolepropionylglycine, indolepropionate, N-methylproline, N-?-acetylornithine), 2 cofactors and vitamins (threonate, oxalate), 1 lipid (chiro-inositol), and 5 xenobiotics (methyl glucopyranoside, stachydrine, catechol sulfate, hippurate, and tartronate). Higher levels of all 13 replicated metabolites were associated with lower NEAP in both AASK and the MDRD study. CONCLUSION:Metabolomic profiling of serum specimens from kidney disease patients in 2 study populations identified 13 replicated metabolites associated with dietary acid load. Additional studies are needed to validate these compounds in healthy populations. These 13 compounds may potentially be used as objective markers of dietary acid load in future nutrition research studies.

SUBMITTER: Rebholz CM

PROVIDER: S-EPMC6461721 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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The Serum Metabolome Identifies Biomarkers of Dietary Acid Load in 2 Studies of Adults with Chronic Kidney Disease.

Rebholz Casey M CM Surapaneni Aditya A Levey Andrew S AS Sarnak Mark J MJ Inker Lesley A LA Appel Lawrence J LJ Coresh Josef J Grams Morgan E ME

The Journal of nutrition 20190401 4

<h4>Background</h4>Dietary acid load is a clinically important aspect of the diet that reflects the balance between acid-producing foods, for example, meat and cheese, and base-producing foods, for example, fruits and vegetables.<h4>Methods</h4>We used metabolomics to identify blood biomarkers of dietary acid load in 2 independent studies of chronic kidney disease patients: the African American Study of Kidney Disease and Hypertension (AASK, n = 689) and the Modification of Diet in Renal Disease ...[more]

PMID: 30919901

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Project description:BackgroundAdvances in metabolomics are anticipated to decipher associations between dietary exposures and health. Replication biomarker studies in different populations are critical to demonstrate generalizability.ObjectivesTo identify and validate robust serum metabolites associated with diet quality and specific foods in a multiethnic cohort of pregnant women.DesignIn this cross-sectional analysis of 3 multiethnic Canadian birth cohorts, we collected semiquantitative FFQ and serum data from 900 women at the second trimester of pregnancy. We calculated a diet quality score (DQS), defined as daily servings of "healthy" minus "unhealthy" foods. Serum metabolomics was performed by multisegment injection-capillary electrophoresis-mass spectrometry, and specific serum metabolites associated with maternal DQSs were identified. We combined the results across all 3 cohorts using meta-analysis to classify robust dietary biomarkers (r > ± 0.1; P < 0.05).ResultsDiet quality was higher in the South Asian birth cohort (mean DQS = 7.1) than the 2 white Caucasian birth cohorts (mean DQS <3.2). Sixty-six metabolites were detected with high frequency (>75%) and adequate precision (CV <30%), and 47 were common to all cohorts. Hippuric acid was positively associated with healthy diet score in all cohorts, and with the overall DQS only in the primarily white Caucasian cohorts. We observed robust correlations between: 1) proline betaine-citrus foods; 2) 3-methylhistidine-red meat, chicken, and eggs; 3) hippuric acid-fruits and vegetables; 4) trimethylamine N-oxide (TMAO)-seafood, meat, and eggs; and 5) tryptophan betaine-nuts/legumes.ConclusionsSpecific serum metabolites reflect intake of citrus fruit/juice, vegetables, animal foods, and nuts/legumes in pregnant women independent of ethnicity, fasting status, and delays to storage across multiple collection centers. Robust biomarkers of overall diet quality varied by cohort. Proline betaine, 3-methylhistidine, hippuric acid, TMAO, and tryptophan betaine were robust dietary biomarkers for investigations of maternal nutrition in diverse populations.

Project description:METHODS:A cross-over study within a split-plot design was performed using healthy (n = 10) and CKD cats [IRIS Stage 1 and 2; n = 10]. Cats were fed dry Prescription Diet® k/d® Feline with chicken, during a pre-trial period and then randomly assigned to two fiber treatments for 4 weeks each. Treatment foods were formulated similar to pre-trial food, with the exception that they contained 0.500% betaine, 0.586% oat beta glucan, and either 0.407% short chain fructooligosaccharides (scFOS) fiber or 3.44% apple pomace. Both foods had similar crude fiber percent (2.0 and 2.1% for scFOS and apple pomace, respectively) whereas soluble fiber was 0.8 and 1.6%, respectively. RESULTS:Plasma metabolites separated cats based on health status. At baseline, cats with CKD had significantly higher circulating concentrations of creatinine, urea, and some microbial and host tryptophan metabolites including several indole sulfates and kynurenate. Healthy cats had higher concentrations of the antioxidant ?-tocopherol after consuming apple pomace; alternatively, they had higher concentrations of inflammatory sphingolipid metabolites after consuming scFOS, but not after consuming apple pomace. The CKD cats had higher concentrations of the more oxidized glutathione metabolites after consuming apple pomace compared with scFOS, as well as higher concentrations of inflammatory sphingolipid metabolites after consuming apple pomace, but not scFOS. After consuming scFOS, CKD cats had lower concentrations of the phenolic uremic toxins guaiacol sulfate and 4-vinylphenol sulfate compared with after consuming apple pomace. At baseline, there were five significant microbiota OTU differences in CKD cats compared with healthy cats. Overall, the OTUs in CKD cats were more resistant to change after feeding either fiber source. Counts of an unclassified genus in the family S24-7 in the order Bacteroidales (OTU 100296), were lower in CKD cats compared with healthy cats at baseline (P = 0.001), but increased after consumption of food containing scFOS (P = 0.006). Linear regression analysis showed that this genus had significant negative correlations with several microbial uremic toxins. None of the baseline differences in OTUs between healthy and CKD cats changed after CKD cats consumed food containing apple pomace. CONCLUSIONS:Health status impacts the influence of dietary fermentable fibers on the feline plasma metabolome and fecal microbiome. A more readily fermented fiber such as scFOS is preferable to apple pomace as a fiber source for cats with CKD.

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The Serum Metabolome Identifies Biomarkers of Dietary Acid Load in 2 Studies of Adults with Chronic Kidney Disease.

Publications

The Serum Metabolome Identifies Biomarkers of Dietary Acid Load in 2 Studies of Adults with Chronic Kidney Disease.

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