TY - JOUR
T1 - Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy
AU - Raines, Nathan H.
AU - Leone, Dominick A.
AU - O’Callaghan-Gordo, Cristina
AU - Ramirez-Rubio, Oriana
AU - Amador, Juan José
AU - Lopez Pilarte, Damaris
AU - Delgado, Iris S.
AU - Leibler, Jessica H.
AU - Embade, Nieves
AU - Gil-Redondo, Rubén
AU - Bruzzone, Chiara
AU - Bizkarguenaga, Maider
AU - Scammell, Madeleine K.
AU - Parikh, Samir M.
AU - Millet, Oscar
AU - Brooks, Daniel R.
AU - Friedman, David J.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/3
Y1 - 2023/3
N2 - Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (n = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (n = 78); Nicaraguans performing non-agricultural work (n = 102); and agricultural workers in Spain (n = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (p = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.
AB - Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (n = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (n = 78); Nicaraguans performing non-agricultural work (n = 102); and agricultural workers in Spain (n = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (p = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.
KW - Mesoamerican nephropathy (MeN)
KW - agriculture
KW - chronic kidney disease of nontraditional cause (CKDnt)
KW - chronic kidney disease of unknown etiology (CKDu)
KW - hippurate
KW - kynurenate
KW - manual labor
KW - nicotinamide adenine dinucleotide (NAD+)
KW - tryptophan
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UR - http://www.scopus.com/inward/citedby.url?scp=85152013271&partnerID=8YFLogxK
U2 - 10.3390/metabo13030325
DO - 10.3390/metabo13030325
M3 - Article
C2 - 36984765
AN - SCOPUS:85152013271
SN - 2218-1989
VL - 13
JO - Metabolites
JF - Metabolites
IS - 3
M1 - 325
ER -