title: Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.
abstract: Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents.
authors.affiliation: Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA, United States.
authors.forename: M
authors.initials: M
authors.lastname: Cárdenas-González
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
authors.forename: C
authors.initials: C
authors.lastname: Osorio-Yáñez
authors.affiliation: Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Unidad Noreste (CIATEJ), Nuevo Leon, Mexico.
authors.forename: O
authors.initials: O
authors.lastname: Gaspar-Ramírez
authors.affiliation: Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA, United States; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States.
authors.forename: M
authors.initials: M
authors.lastname: Pavković
authors.affiliation: Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Ochoa-Martínez
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), México City, Mexico.
authors.forename: D
authors.initials: D
authors.lastname: López-Ventura
authors.affiliation: Departamento de Nefrología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico; Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Medeiros
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), México City, Mexico.
authors.forename: O C
authors.initials: OC
authors.lastname: Barbier
authors.affiliation: Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico.
authors.forename: I N
authors.initials: IN
authors.lastname: Pérez-Maldonado
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States.
authors.forename: V S
authors.initials: VS
authors.lastname: Sabbisetti
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States.
authors.forename: J V
authors.initials: JV
authors.lastname: Bonventre
authors.affiliation: Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA, United States; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States. Electronic address: vvaidya@bwh.harvard.edu.
authors.forename: V S
authors.initials: VS
authors.lastname: Vaidya
mesh_terms: D001151:Arsenic / Q000032:analysis / Q000097:blood / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002857:Chromium / Q000032:analysis / Q000097:blood / Q000652:urine*; D003404:Creatinine / Q000097:blood; D060766:Drinking Water / Q000032:analysis; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000032:analysis / Q000097:blood / Q000652:urine*; D005260:Female; D005459:Fluorides / Q000032:analysis / Q000097:blood / Q000652:urine; D005919:Glomerular Filtration Rate; D060587:Groundwater / Q000032:analysis; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000652:urine; D007854:Lead / Q000032:analysis / Q000097:blood / Q000652:urine; D000071068:Lipocalin-2 / Q000652:urine; D008297:Male; D008800:Mexico; D035683:MicroRNAs / Q000652:urine; D012709:Serum Albumin / Q000032:analysis
chemical_list: D015415:Biomarkers; D060766:Drinking Water; D004785:Environmental Pollutants; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; C533896:MIRN200 microRNA, human; C524940:MIRN21 microRNA, human; C548900:MIRN423 microRNA, human; D035683:MicroRNAs; D012709:Serum Albumin; D002857:Chromium; D007854:Lead; D003404:Creatinine; D001151:Arsenic; D005459:Fluorides
keywords: Arsenic; Children; Chromium; KIM-1; miRNAs