{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:07:16Z","timestamp":1789074436203,"version":"build-2803163510"},"reference-count":129,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:00:00Z","timestamp":1769299200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute of Environmental Health Sciences ViCTER","award":["R01ES033466"],"award-info":[{"award-number":["R01ES033466"]}]},{"name":"Superfund","award":["P42-ES010356"],"award-info":[{"award-number":["P42-ES010356"]}]},{"name":"Superfund","award":["T32-ES021432"],"award-info":[{"award-number":["T32-ES021432"]}]},{"name":"Duke Global Health Institute and Nicholas School of the Environment Pilot Grant funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic kidney disease (CKD) affects \u223c15% of US adults and over 840 million people worldwide. Environmental contaminants, including pesticides and metals, are increasingly recognized as disease contributors, yet mechanisms and consequences of long-term, low-level mixture exposures remain poorly defined. Our prior work identified glyphosate and metals (cadmium, arsenic, lead, and vanadium) in drinking water from agricultural regions with high CKD prevalence and showed that early-life co-exposures disrupt kidney development. Here, using adult zebrafish as a mechanistic model, we tested whether chronic, low-level exposure to glyphosate, metals, and their combination impairs kidney function and structure. We exposed zebrafish for 10 and 60\u2009days to glyphosate (10\u2009ppb), metals (2\u2009ppb Cd, 4\u2009ppb As, 5\u2009ppb Pb, 15\u2009V), or glyphosate + metals and evaluated low-molecular-weight proteinuria, histopathology, metabolomics, mitochondrial function, mitochondrial copy number, and mitophagy in the kidney. Chronic exposure to glyphosate and metals produced distinct yet overlapping kidney toxicity signatures, including tubular injury, altered metabolism, and impaired mitochondrial function. Co-exposures generated the most severe effects, with mitochondrial beta oxidation, respiration, and mitophagy as sensitive targets. These findings demonstrate that glyphosate and metals at levels found in drinking water damage kidney function over time, with co-exposure worsening outcomes compared with individual chemicals. Our study identifies mitochondria-rich proximal tubules as critical targets of chronic glyphosate\u2013metal exposure, providing mechanistic insight into how environmental contaminants contribute to CKD risk. This work advances understanding of disease etiology in environmental nephropathies and highlights environmental factors as important drivers of kidney health.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag007","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T12:53:13Z","timestamp":1769086393000},"source":"Crossref","is-referenced-by-count":3,"title":["Chronic exposure to low levels of glyphosate and metals induces kidney dysfunction"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0612-7400","authenticated-orcid":false,"given":"Ilaria R","family":"Merutka","sequence":"first","affiliation":[{"name":"Nicholas School of the Environment, Duke University , Durham, NC 27710,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3614-659X","authenticated-orcid":false,"given":"Kerry 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Silva","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science, University of Ruhuna , Matara, 81000, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3734-1231","authenticated-orcid":false,"given":"Iain A","family":"Drummond","sequence":"additional","affiliation":[{"name":"Mount Desert Island Biological Laboratories , Bar Harbor, ME 04609,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-6893","authenticated-orcid":false,"given":"Nishad","family":"Jayasundara","sequence":"additional","affiliation":[{"name":"Nicholas School of the Environment, Duke University , Durham, NC 27710,","place":["United 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