Urinary metabolomic profile of youth at risk of chronic kidney disease in Nicaragua

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• dc.contributor.author Hall, Samantha M.
• dc.contributor.author Raines, Nathan H.
• dc.contributor.author Ramirez Rubio, Oriana
• dc.contributor.author Amador, Juan José
• dc.contributor.author López-Pilarte, Damaris
• dc.contributor.author O'Callaghan-Gordo, Cristina
• dc.contributor.author Gil-Redondo, Rubén
• dc.contributor.author Embade, Nieves
• dc.contributor.author Millet, Oscar
• dc.contributor.author Peng, Xiaojing
• dc.contributor.author Vences, Selene
• dc.contributor.author Keogh, Sinead A.
• dc.contributor.author Delgado, Iris
• dc.contributor.author Friedman, David J.
• dc.contributor.author Brooks, Daniel R.
• dc.contributor.author Leibler, Jessica H.
• dc.date.accessioned 2023-11-27T07:13:59Z
• dc.date.available 2023-11-27T07:13:59Z
• dc.date.issued 2023
• dc.description.abstract Background: CKD of a nontraditional etiology (CKDnt) is responsible for high mortality in Central America, although its causes remain unclear. Evidence of kidney dysfunction has been observed among youth, suggesting that early kidney damage contributing to CKDnt may initiate in childhood. Methods: Urine specimens of young Nicaraguan participants 12–23 years without CKDnt (n=136) were analyzed by proton nuclear magnetic resonance spectroscopy for 50 metabolites associated with kidney dysfunction. Urinary metabolite levels were compared by, regional CKDnt prevalence, sex, age, and family history of CKDnt using supervised statistical methods and pathway analysis in MetaboAnalyst. Magnitude of associations and changes over time were assessed through multivariable linear regression. Results: In adjusted analyses, glycine concentrations were higher among youth from high-risk regions (β=0.82, [95% confidence interval, 0.16 to 1.85]; P = 0.01). Pyruvate concentrations were lower among youth with low eGFR (β= −0.36 [95% confidence interval, −0.57 to −0.04]; P = 0.03), and concentrations of other citric acid cycle metabolites differed by key risk factors. Over four years, participants with low eGFR experienced greater declines in 1-methylnicotinamide and 2-oxoglutarate and greater increases in citrate and guanidinoacetate concentrations. Conclusion: Urinary concentration of glycine, a molecule associated with thermoregulation and kidney function preservation, was higher among youth in high-risk CKDnt regions, suggestive of greater heat exposure or renal stress. Lower pyruvate concentrations were associated with low eGFR, and citric acid cycle metabolites, such as pyruvate, likely relate to mitochondrial respiration rates in the kidneys. Participants with low eGFR experienced longitudinal declines in concentrations of 1-methylnicotinamide, an anti-inflammatory metabolite associated with anti-fibrosis in tubule cells. These findings merit further consideration in research on the origins of CKDnt.
• dc.description.sponsorship This study was funded by the Fundación Renal Iñigo Alvarez de Toledo (FRIAT Foundation), Spain (PI: Brooks), and NIH/NIEHS NIH R01ES031606 (PI: Leibler). S. Hall was supported by training grants from the National Science Foundation (NRT DGE 1735087) and NIH/NIEHS (2T32ES014562-16). N.H. Raines is supported by the Doris Duke Charitable Foundation Physician Scientist Fellowship Award Grant #202182. The funders had no role in study design, collection, analysis, and interpretation of data or in the preparation or writing of this manuscript.
• dc.format.mimetype application/pdf
• dc.identifier.citation Hall SM, Raines NH, Ramirez-Rubio O, Amador JJ, López-Pilarte D, O'Callaghan-Gordo C, Gil-Redondo R, Embade N, Millet O, Peng X, Vences S, Keogh SA, Delgado IS, Friedman DJ, Brooks DR, Leibler JH. Urinary metabolomic profile of youth at risk of chronic kidney disease in Nicaragua. Kidney360. 2023 Jul 1;4(7):899-908. DOI: 10.34067/KID.0000000000000129
• dc.identifier.doi http://dx.doi.org/10.34067/KID.0000000000000129
• dc.identifier.issn 2641-7650
• dc.identifier.uri http://hdl.handle.net/10230/58373
• dc.language.iso eng
• dc.publisher Wolters Kluwer (LWW)
• dc.relation.ispartof Kidney360. 2023 Jul 1;4(7):899-908
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/202182
• dc.rights © 2023 The Author(s). Published by Wolters KluwerHealth, Inc. on behalf of the American Society of Nephrology. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Chronic kidney disease
• dc.subject.keyword Occupational health
• dc.subject.keyword Central America
• dc.subject.keyword CKDu
• dc.subject.keyword CKDnt
• dc.subject.keyword Mesoamerican nephropathy
• dc.subject.keyword Pediatric kidney disease
• dc.subject.keyword Adolescent
• dc.subject.keyword Epidemiology
• dc.subject.keyword Metabolomics
• dc.subject.keyword Nicaragua
• dc.subject.keyword Occupational health
• dc.title Urinary metabolomic profile of youth at risk of chronic kidney disease in Nicaragua
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion