{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:54:50Z","timestamp":1791572090245,"version":"4.3.4"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Exposure to heavy metals (cadmium, mercury, and lead) has been linked with adverse health outcomes, especially their nephrotoxic effects at high levels of exposure. We conducted a replication study to examine the association of low-level heavy metal exposure and chronic kidney disease (CKD) using a larger NHANES data set compared to previous studies.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The large cross-sectional study comprised 5,175 CKD cases out of 55677 participants aged 20\u201385 years from the 1999\u20132020 National Health and Nutrition Examination Survey [NHANES]. Logistic regression analysis was applied to estimate the associations between CKD and heavy metals [Cd, Pb, Hg] measured as categorical variables after adjusting with age, race, gender, socioeconomic status, hypertension, diabetes mellitus and blood cotinine level as smoking status.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compared to the lowest quartile of blood Cd, exposures to the 2<jats:sup>nd<\/jats:sup>, 3<jats:sup>rd<\/jats:sup> and 4<jats:sup>th<\/jats:sup> quartiles of blood Cd were statistically significantly associated with higher odds of CKD after adjustment for blood Pb and Hg, with OR = 1.79, [95% CI; 1.55\u20132.07, p&lt;0.0001], OR = 2.17, [95% CI; 1.88\u20132.51, p&lt;0.0001] and OR = 1.52, [95% CI; 1.30\u20131.76, p&lt;0.0001] respectively. The 2<jats:sup>nd<\/jats:sup>, 3<jats:sup>rd<\/jats:sup> and 4<jats:sup>th<\/jats:sup> quartiles of blood Cd remained statistically significantly associated with higher odds of CKD after adjustment for blood cotinine level, with OR = 2.06, [95% CI; 1.80\u20132.36, p&lt;0.0001], OR = 3.18, [95% CI; 2.79\u20133.63, p&lt;0.0001] and OR = 5.54, [95% CI; 4.82\u20136.37, p&lt;0.0001] respectively. Exposure to blood Pb was statistically significantly associated with higher odds of CKD in the 2<jats:sup>nd<\/jats:sup>, 3<jats:sup>rd<\/jats:sup> and 4<jats:sup>th<\/jats:sup> quartile groups, after adjustment for all co-variates (ag, gender, race, socio-economic status, hypertension, diabetes mellitus, blood cadmium, mercury, and cotinine levels) in all the four models. Blood Hg level was statistically significantly associated with lower odds of CKD in the 2<jats:sup>nd<\/jats:sup> quartile group in model 2, 3<jats:sup>rd<\/jats:sup> quartile group in model 1, 2 and 3, and the 4<jats:sup>th<\/jats:sup> quartile group in all the four models.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our findings showed that low blood levels of Cd and Pb were associated with higher odds of CKD while low blood levels of Hg were associated with lower odds of CKD in the US adult population. However, temporal association cannot be determined as it is a cross sectional study.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0288190","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T17:35:22Z","timestamp":1713288922000},"page":"e0288190","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Exposure to low levels of heavy metals and chronic kidney disease in the US population: A cross sectional study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9382-3368","authenticated-orcid":true,"given":"Akintayo","family":"Akinleye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olayinka","family":"Oremade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"pone.0288190.ref001","unstructured":"Centers for Disease Control and Prevention: Lead Factsheet. https:\/\/www.cdc.gov\/biomonitoring\/Lead_FactSheet.html. Accessed March 27, 2023."},{"key":"pone.0288190.ref002","unstructured":"Centers for Disease Control and Prevention: Cadmium Factsheet. https:\/\/www.cdc.gov\/biomonitoring\/Cadmium_FactSheet.html. Accessed March 27, 2023."},{"key":"pone.0288190.ref003","unstructured":"Centers for Disease Control and Prevention: Mercury Factsheet. https:\/\/www.cdc.gov\/biomonitoring\/Mercury_FactSheet.html. Accessed March 27, 2023."},{"key":"pone.0288190.ref004","unstructured":"ATSDR. (1999, March). Toxicological Profile for Mercury. April 5, 2016, http:\/\/www.atsdr.cdc.gov\/toxprofiles\/tp46.pdf"},{"key":"pone.0288190.ref005","unstructured":"ATSDR. (2012, September). Toxicological Profile for Cadmium. April 5, 2016, http:\/\/www.atsdr.cdc.gov\/toxprofiles\/tp5.pdf"},{"key":"pone.0288190.ref006","unstructured":"ATSDR. (2007, August). Toxicological Profile for Lead. April 5, 2016, http:\/\/www.atsdr.cdc.gov\/toxprofiles\/tp13.pdf"},{"issue":"2","key":"pone.0288190.ref007","first-page":"5","article-title":"National vital statistics reports","volume":"64","author":"X Jiaquan","year":"2016","journal-title":"Deaths: Final Data for 2013"},{"key":"pone.0288190.ref008","unstructured":"National Kidney Foundation (2023). Kidney disease: The Basics. March 29, 2023 kidney.org\/news\/newsroom\/fsindex"},{"issue":"4","key":"pone.0288190.ref009","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/01913120309921","article-title":"Dose-dependent mercuric chloride tubular injury in rat kidney","volume":"27","author":"A Stacchiotti","year":"2003","journal-title":"Ultrastructural Pathology"},{"issue":"3","key":"pone.0288190.ref010","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.toxlet.2015.07.018","article-title":"Cadmium chloride inhibits lactate gluconeogenesis in mouse renal proximal tubules: an in vitro metabolomic approach with 13C NMR","volume":"238","author":"H Faiz","year":"2015","journal-title":"Toxicology letters"},{"issue":"9","key":"pone.0288190.ref011","doi-asserted-by":"crossref","first-page":"705","DOI":"10.3109\/15376516.2012.718811","article-title":"Oxidative stress: a possible mechanism for lead-induced apoptosis and nephrotoxicity","volume":"22","author":"Q Jia","year":"2012","journal-title":"Toxicology mechanisms and methods"},{"issue":"9","key":"pone.0288190.ref012","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"AS Levey","year":"2009","journal-title":"Annals of internal medicine"},{"issue":"6","key":"pone.0288190.ref013","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":"AS Levey","year":"2005","journal-title":"Kidney international"},{"issue":"9","key":"pone.0288190.ref014","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1093\/aje\/kwp248","article-title":"Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis","volume":"170","author":"A Navas-Acien","year":"2009","journal-title":"American journal of epidemiology"},{"issue":"1","key":"pone.0288190.ref015","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/1471-2458-10-304","article-title":"Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999\u20132006","volume":"10","author":"PM Ferraro","year":"2010","journal-title":"BMC Public Health"},{"issue":"3","key":"pone.0288190.ref016","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ijheh.2016.01.005","article-title":"Urinary and blood cadmium and lead and kidney function: NHANES 2007\u20132012","volume":"219","author":"MC Buser","year":"2016","journal-title":"Int J Hyg Environ Health"},{"key":"pone.0288190.ref017","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.envres.2018.11.009","article-title":"Associations between blood cadmium concentration and kidney function in the U.S. population: Impact of sex, diabetes and hypertension","volume":"169","author":"JM Madrigal","year":"2019","journal-title":"Environ Res"},{"issue":"3","key":"pone.0288190.ref018","doi-asserted-by":"crossref","first-page":"272","DOI":"10.3346\/jkms.2015.30.3.272","article-title":"Environmental heavy metal exposure and chronic kidney disease in the general population","volume":"30","author":"NH Kim","year":"2015","journal-title":"Journal of Korean medical science"},{"issue":"2","key":"pone.0288190.ref019","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":"C Jalili","year":"2021","journal-title":"Critical Reviews in Toxicology"},{"issue":"8","key":"pone.0288190.ref020","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1289\/ehp.1205164","article-title":"Blood lead level and measured glomerular filtration rate in children with chronic kidney disease","volume":"121","author":"JJ Fadrowski","year":"2013","journal-title":"Environmental health perspectives"},{"key":"pone.0288190.ref021","doi-asserted-by":"crossref","first-page":"1","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":"JN Sommar","year":"2013","journal-title":"Environmental health"},{"issue":"5","key":"pone.0288190.ref022","doi-asserted-by":"crossref","first-page":"475","DOI":"10.3109\/0886022X.2011.577922","article-title":"Investigation of the relationship between serum levels of cotinine and the renal function in active and passive smokers","volume":"33","author":"H D\u00fclger","year":"2011","journal-title":"Renal failure"},{"key":"pone.0288190.ref023","doi-asserted-by":"crossref","first-page":"870278","DOI":"10.3389\/fmed.2022.870278","article-title":"The association between smoking and renal function in people over 20 years old","volume":"9","author":"YC Fu","year":"2022","journal-title":"Frontiers in Medicine"},{"key":"pone.0288190.ref024","unstructured":"NCHS. (2008). National Health and Nutritional Examination Survey. April 12, 2016 http:\/\/www.cdc.gov\/nchs\/nhanes.htm"},{"issue":"4","key":"pone.0288190.ref025","first-page":"557","article-title":"Cadmium & its adverse effects on human health","volume":"128","author":"A Bernard","year":"2008","journal-title":"Indian Journal of Medical Research"},{"issue":"12","key":"pone.0288190.ref026","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.3168\/jds.S0022-0302(75)84785-0","article-title":"Metabolism and toxicity of cadmium, mercury, and lead in animals: a review","volume":"58","author":"MW Neathery","year":"1975","journal-title":"Journal of dairy science"},{"key":"pone.0288190.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12011-018-1509-5","article-title":"Association between exposure to heavy metals and systemic sclerosis: the levels of Al, Cd, Hg, and Pb in blood and urine of patients","volume":"190","author":"G Forte","year":"2019","journal-title":"Biological Trace Element Research"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0288190","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T17:35:39Z","timestamp":1713288939000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0288190"}},"subtitle":[],"editor":[{"given":"Iman","family":"Al-Saleh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0288190","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]}}}