TY - JOUR
T1 - Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population
AU - Reynolds, Kaylia M.
AU - Lin, Bridget M.
AU - Armstrong, Nicole D.
AU - Ottosson, Filip
AU - Zhang, Ying
AU - Williams, Ashley S.
AU - Yu, Bing
AU - Boerwinkle, Eric
AU - Thygarajan, Bharat
AU - Daviglus, Martha L.
AU - Muoio, Deborah
AU - Qi, Qibin
AU - Kaplan, Robert
AU - Melander, Olle
AU - Lash, James P.
AU - Cai, Jianwen
AU - Irvin, Marguerite R.
AU - Newgard, Christopher B.
AU - Sofer, Tamar
AU - Franceschini, Nora
N1 - Publisher Copyright:
Copyright © 2022 by the American Society of Nephrology.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - BACKGROUND: Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanic/Latino people, a population with high risk for metabolic disease. METHODS: We used data from 3736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin-to-creatinine ratio (UACR). Metabolites were quantified in fasting serum through nontargeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites, in covariate-adjusted models that accounted for the study design. In total, 132 metabolites were available for replication in the Hypertension Genetic Epidemiology Network study ( n =300), and 29 metabolites were available for replication in the Malmö Offspring Study ( n =999). RESULTS: Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-glutamine and D-glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism. CONCLUSIONS: Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanic/Latino population. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_02_08_CJN09070822.mp3.
AB - BACKGROUND: Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanic/Latino people, a population with high risk for metabolic disease. METHODS: We used data from 3736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin-to-creatinine ratio (UACR). Metabolites were quantified in fasting serum through nontargeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites, in covariate-adjusted models that accounted for the study design. In total, 132 metabolites were available for replication in the Hypertension Genetic Epidemiology Network study ( n =300), and 29 metabolites were available for replication in the Malmö Offspring Study ( n =999). RESULTS: Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-glutamine and D-glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism. CONCLUSIONS: Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanic/Latino population. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_02_08_CJN09070822.mp3.
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U2 - 10.2215/CJN.09070822
DO - 10.2215/CJN.09070822
M3 - Article
C2 - 36517247
AN - SCOPUS:85147783314
SN - 1555-9041
VL - 18
SP - 204
EP - 212
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
IS - 2
ER -
