{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:38:10Z","timestamp":1790786290374,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["R16GM149473"],"award-info":[{"award-number":["R16GM149473"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Exposure to environmental pollutants, including toxic metals, volatile organic compounds (VOCs), and per- and polyfluoroalkyl substances (PFAS), has been increasingly linked to impaired kidney function. However, the combined effects of these exposures, along with essential elements, on kidney health remain poorly understood. This study aimed to evaluate the independent and cumulative or mixture effects of toxic metals (cadmium, lead, and mercury), essential elements (iron, manganese, and selenium), PFAS (PFOA and PFOS), and VOCs (m-\/p-xylene and o-xylene) on kidney function as measured by estimated glomerular filtration rate (eGFR). Using data from the National Health and Nutrition Examination Survey (NHANES), we applied multiple imputation to address missing data and implemented statistical techniques, including Bayesian Kernel Machine Regression (BKMR), quantile g-computation, and Weighted Quantile Sum Regression (WQSR) to assess complex exposure\u2013response relationships, including non-linear, potential synergistic, and antagonistic effects. The results indicated that several exposures were correlated, particularly o-xylene with m-\/p-xylene (r = 0.77), Cd with Pb (r = 0.46), and PFOS with PFOA (r = 0.61). eGFR was negatively associated with Pb, PFOS, PFOA, and Hg. In the BKMR analysis, overall posterior inclusion probabilities (PIPs) highlighted PFOS, Cd, Se, Mn, and Fe as the most influential exposures. Quantile g-computation highlighted Cd and Mn as major contributors, while WQSR modeling confirmed Mn as a key contributor. The findings underscore the importance of considering complex interactions in environmental exposure assessments. While essential elements may offer protective effects, toxic metals, PFAS, and VOCs remain critical contributors to kidney dysfunction. These insights highlight the need for integrative risk assessment approaches and public health strategies aimed at mitigating harmful exposures while promoting optimal nutrient balance.<\/jats:p>","DOI":"10.3390\/jox15060202","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:39:43Z","timestamp":1764679183000},"page":"202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigation of Combined Toxic Metals, PFAS, Volatile Organic Compounds, and Essential Elements in Chronic Kidney Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Aderonke Gbemi","family":"Adetunji","sequence":"first","affiliation":[{"name":"Department of Built Environment, North Carolina A&T State University, Greensboro, NC 27411, USA"},{"name":"Environmental Health and Disease Laboratory, North Carolina A&T State University, Greensboro, NC 27411, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3195-706X","authenticated-orcid":false,"given":"Emmanuel","family":"Obeng-Gyasi","sequence":"additional","affiliation":[{"name":"Department of Built Environment, North Carolina A&T State University, Greensboro, NC 27411, USA"},{"name":"Environmental Health and Disease Laboratory, North Carolina A&T State University, Greensboro, NC 27411, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41572-024-00589-9","article-title":"Chronic Kidney Disease","volume":"11","author":"Romagnani","year":"2025","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of Chronic Kidney Disease: An Update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int. Suppl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3390\/kidneydial3020017","article-title":"The Importance of Lifestyle Interventions in the Prevention and Treatment of Chronic Kidney Disease","volume":"3","author":"Castle","year":"2023","journal-title":"Kidney Dial."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1093\/ndt\/gfz174","article-title":"A Single Number for Advocacy and Communication\u2014Worldwide More Than 850 Million Individuals Have Kidney Diseases","volume":"34","author":"Jager","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_5","unstructured":"Centers for Disease Control and Prevention (CDC) (2025, November 26). Chronic Kidney Disease in the United States, 2023, Available online: https:\/\/www.cdc.gov\/kidney-disease\/php\/data-research\/index.html."},{"key":"ref_6","first-page":"1","article-title":"Functions of Kidney & Artificial Kidneys","volume":"1","author":"Raghavendra","year":"2013","journal-title":"Int. J. Innov. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0140-6736(11)60178-5","article-title":"Chronic Kidney Disease","volume":"379","author":"Levey","year":"2012","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S0140-6736(21)00519-5","article-title":"Chronic Kidney Disease","volume":"398","author":"Jafar","year":"2021","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17088","DOI":"10.1038\/nrdp.2017.88","article-title":"Chronic Kidney Disease","volume":"3","author":"Romagnani","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_10","first-page":"00179","article-title":"Glomerulonephritis Contributing to Chronic Kidney Disease","volume":"5","author":"Naqvi","year":"2017","journal-title":"Urol. Nephrol. Open Access J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41572-018-0047-y","article-title":"Polycystic Kidney Disease","volume":"4","author":"Bergmann","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhang, X., Donnan, P.T., Bell, S., and Guthrie, B. (2017). Non-Steroidal Anti-Inflammatory Drug Induced Acute Kidney Injury in the Community Dwelling General Population and People with Chronic Kidney Disease: Systematic Review and Meta-Analysis. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0673-8"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wimalawansa, S.J., and Dissanayake, C.B. (2019). Factors Affecting the Environmentally Induced, Chronic Kidney Disease of Unknown Aetiology in Dry Zonal Regions in Tropical Countries\u2014Novel Findings. Environments, 7.","DOI":"10.3390\/environments7010002"},{"key":"ref_14","first-page":"294","article-title":"Chronic Kidney Disease of Nontraditional Etiology in Central America: A Provisional Epidemiologic Case Definition for Surveillance and Epidemiologic Studies","volume":"40","author":"Lozier","year":"2016","journal-title":"Rev. Panam. Salud P\u00fablica"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1111\/j.1523-1755.2005.00365.x","article-title":"Definition and Classification of Chronic Kidney Disease: A Position Statement from Kidney Disease: Improving Global Outcomes (KDIGO)","volume":"67","author":"Levey","year":"2005","journal-title":"Kidney Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1023\/A:1017918013293","article-title":"Molecular Mechanisms of Metal Toxicity and Carcinogenesis","volume":"222","author":"Wang","year":"2001","journal-title":"Mol. Cell. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Haruna, I., and Obeng-Gyasi, E. (2024). Association of Combined Per- and Polyfluoroalkyl Substances and Metals with Chronic Kidney Disease. Int. J. Environ. Res. Public Health, 21.","DOI":"10.3390\/ijerph21040468"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/10408444.2021.1891196","article-title":"Associations between Exposure to Heavy Metals and the Risk of Chronic Kidney Disease: A Systematic Review and Meta-Analysis","volume":"51","author":"Jalili","year":"2021","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tsai, H.-J., Hung, C.-H., Wang, C.-W., Tu, H.-P., Li, C.-H., Tsai, C.-C., Lin, W.-Y., Chen, S.-C., and Kuo, C.-H. (2021). Associations Among Heavy Metals and Proteinuria and Chronic Kidney Disease. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020282"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Akinleye, A., Oremade, O., and Xu, X. (2024). Exposure to Low Levels of Heavy Metals and Chronic Kidney Disease in the U.S. Population: A Cross-Sectional Study. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0288190"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2147\/DMSO.S173809","article-title":"Perfluoroalkyl Substances and Kidney Function in Chronic Kidney Disease, Anemia, and Diabetes","volume":"11","author":"Conway","year":"2018","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000517711","article-title":"The Role of Perfluorinated Compound Pollution in the Development of Acute and Chronic Kidney","volume":"Volume 199","author":"Roncob","year":"2021","journal-title":"Nephrology and Public Health Worldwide"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, D., Yan, S., Wang, P., Chen, Q., Liu, Y., Cui, J., Liang, Y., Ren, S., and Gao, Y. (2023). Perfluorooctanoic Acid (PFOA) Exposure in Relation to the Kidneys: A Review of Current Available Literature. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1103141"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.2215\/CJN.04670418","article-title":"Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health: A Scoping Review","volume":"13","author":"Stanifer","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, Y., Gao, N., Gong, Y., Shi, W., and Wang, X. (2023). Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411503"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10258","DOI":"10.1021\/acs.est.1c08298","article-title":"Home Is Where the Pipeline Ends: Characterization of Volatile Organic Compounds Present in Natural Gas at the Point of the Residential End User","volume":"56","author":"Michanowicz","year":"2022","journal-title":"Environ. Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7491","DOI":"10.5194\/acp-9-7491-2009","article-title":"Vehicular Emission of Volatile Organic Compounds (VOCs) from a Tunnel Study in Hong Kong","volume":"9","author":"Ho","year":"2009","journal-title":"Atmos. Chem. Phys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/mas.20119","article-title":"Measurements of Volatile Organic Compounds in the Earth\u2019s Atmosphere Using Proton-Transfer-Reaction Mass Spectrometry","volume":"26","author":"Warneke","year":"2007","journal-title":"Mass Spectrom. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4236\/jep.2011.21003","article-title":"Ambient Air Non-Methane Volatile Organic Compound (NMVOC) Study Initiatives in India\u2014A Review","volume":"2","author":"Talapatra","year":"2011","journal-title":"J. Environ. Prot."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00420-005-0001-7","article-title":"Occupational Exposure to Toluene and Its Possible Causative Role in Renal Damage Development in Shoe Workers","volume":"79","author":"Kazimierz","year":"2006","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s00420-009-0398-5","article-title":"Effects of Occupational Exposure to 1,4-Dichlorobenzene on Hematologic, Kidney, and Liver Functions","volume":"82","author":"Hsiao","year":"2009","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jankowska, M., Rutkowski, B., and D\u0119bska-\u015alizie\u0144, A. (2017). Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease. Nutrients, 9.","DOI":"10.3390\/nu9030282"},{"key":"ref_33","first-page":"405","article-title":"The Trinity of Essential Trace Elements (TEs) Imbalance, Oxidative Stress (OS) and Inflammatory State in Chronic Kidney Disease and Hemodialysis (HD) Patients: Vicious Triad for Disease Progression and Outcomes","volume":"62","author":"Delipavlova","year":"2024","journal-title":"Knowl.-Int. J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Davenport, A. (2015). Trace elements in patients with chronic kidney disease. Chronic Renal Disease, Elsevier.","DOI":"10.1016\/B978-0-12-411602-3.00036-6"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5414\/CN110322","article-title":"Principles Responsible for Trace Element Concentrations in Chronic Kidney Disease","volume":"96","author":"Filler","year":"2021","journal-title":"Clin. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fukasawa, H., Furuya, R., Kaneko, M., Nakagami, D., Ishino, Y., Kitamoto, S., Omata, K., and Yasuda, H. (2023). Clinical Significance of Trace Element Zinc in Patients with Chronic Kidney Disease. J. Clin. Med., 12.","DOI":"10.3390\/jcm12041667"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"126809","DOI":"10.1016\/j.chemosphere.2020.126809","article-title":"Plasma Element Levels and Risk of Chronic Kidney Disease in Elderly Populations (\u226590 Years Old)","volume":"254","author":"Shen","year":"2020","journal-title":"Chemosphere"},{"key":"ref_38","unstructured":"Centers for Disease Control and Prevention (CDC) (2025, October 23). Laboratory Methods; NHANES 2017\u20132018, Available online: https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/continuousnhanes\/labmethods.aspx?BeginYear=2017."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/mpr.329","article-title":"Multiple Imputation by Chained Equations: What Is It and How Does It Work?","volume":"20","author":"Azur","year":"2011","journal-title":"Int. J. Methods Psychiatr. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/biostatistics\/kxu058","article-title":"Bayesian Kernel Machine Regression for Estimating the Health Effects of Multi-Pollutant Mixtures","volume":"16","author":"Bobb","year":"2015","journal-title":"Biostatistics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12940-018-0413-y","article-title":"Statistical Software for Analyzing the Health Effects of Multiple Concurrent Exposures via Bayesian Kernel Machine Regression","volume":"17","author":"Bobb","year":"2018","journal-title":"Environ. Health"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Akinbode, O.L., and Obeng-Gyasi, E. (2025). Combined Effects of Arsenic, Cadmium, and Mercury with Cardiovascular Disease Risk: Insights from the All of Us Research Program. Int. J. Environ. Res. Public Health, 22.","DOI":"10.3390\/ijerph22020239"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s40572-017-0162-z","article-title":"Statistical Approaches to Address Multi-Pollutant Mixtures and Multiple Exposures: The State of the Science","volume":"4","author":"Tafoggia","year":"2017","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Adetunji, A.G., and Obeng-Gyasi, E. (2024). Investigating the Interplay of Toxic Metals and Essential Elements in Liver Disease. Int. J. Environ. Res. Public Health, 21.","DOI":"10.3390\/ijerph21060762"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Adetunji, A.G., and Obeng-Gyasi, E. (2025). Investigating the Interplay of Toxic Metals and Essential Elements in Cardiovascular Disease. J. Xenobiot., 15.","DOI":"10.3390\/jox15030068"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108","DOI":"10.5001\/omj.2012.23","article-title":"Estimated Glomerular Filtration Rate (eGFR): A Serum Creatinine-Based Test for the Detection of Chronic Kidney Disease and Its Impact on Clinical Practice","volume":"27","year":"2012","journal-title":"Oman Med. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1021\/es071148m","article-title":"A General Approach to Modeling Biphasic Relationships","volume":"42","author":"Beckon","year":"2008","journal-title":"Environ. Sci. Technol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, J., Zhang, X., Chen, Y., Chen, X., and Zhang, Y. (2022). The Relationship between Typical Environmental Endocrine Disruptors and Kidney Disease. Ecotoxicol. Environ. Saf., 11.","DOI":"10.3390\/toxics11010032"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1476-069X-12-9","article-title":"End-Stage Renal Disease and Low-Level Exposure to Lead, Cadmium and Mercury: A Population-Based, Prospective Nested Case-Referent Study in Sweden","volume":"12","author":"Sommar","year":"2013","journal-title":"Environ. Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"047004","DOI":"10.1289\/EHP5838","article-title":"A Quantile-Based g-Computation Approach to Addressing the Effects of Exposure Mixtures","volume":"128","author":"Keil","year":"2020","journal-title":"Environ. Health Perspect."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1111\/jch.13673","article-title":"Synergistic Interaction of Hypertension and Hyperhomocysteinemia on Chronic Kidney Disease: Findings from the National Health and Nutrition Examination Survey 1999\u20132006","volume":"21","author":"Shi","year":"2019","journal-title":"J. Clin. Hypertens."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"087010","DOI":"10.1289\/EHP10570","article-title":"A Permutation Test-Based Approach to Strengthening Inference on the Effects of Environmental Mixtures: Comparison between Single-Index Analytic Methods","volume":"130","author":"Day","year":"2022","journal-title":"Environ. Health Perspect."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Xu, J.-J., Chen, J.-L., Jiang, W.-D., Liu, Y., Feng, L., Wu, P., and Zhou, X.-Q. (2023). Influences of Five Dietary Manganese Sources on Growth, Feed Utilization, Lipid Metabolism, Antioxidant Capacity, Inflammatory Response and Endoplasmic Reticulum Stress in Yellow Catfish Intestine. Front. Physiol., 566.","DOI":"10.1016\/j.aquaculture.2022.739190"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"gfae069-0502-1054","DOI":"10.1093\/ndt\/gfae069.502","article-title":"Dietary Manganese Intake and Risk of Chronic Kidney Disease: Insights from the UK Biobank Study","volume":"39","author":"Park","year":"2024","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_55","first-page":"103138","article-title":"Association of Dietary Manganese Intake with New-Onset Chronic Kidney Disease in Participants with Diabetes","volume":"18","author":"Huang","year":"2024","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_56","first-page":"934","article-title":"Exposure to Volatile Organic Compounds and Kidney Dysfunction in Thin Film Transistor Liquid Crystal Display (TFT-LCD) Workers","volume":"178","author":"Chang","year":"2010","journal-title":"Toxicol. Appl. Pharmacol."}],"container-title":["Journal of Xenobiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4713\/15\/6\/202\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T13:22:16Z","timestamp":1764681736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4713\/15\/6\/202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":56,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["jox15060202"],"URL":"https:\/\/doi.org\/10.3390\/jox15060202","relation":{},"ISSN":["2039-4713"],"issn-type":[{"value":"2039-4713","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]}}}