{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:45:48Z","timestamp":1774874748828,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T00:00:00Z","timestamp":1689379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>The excretion of \u03b22-microglobulin (\u03b22M) above 300 \u00b5g\/g creatinine, termed tubulopathy, was regarded as the critical effect of chronic exposure to the metal pollutant cadmium (Cd). However, current evidence suggests that Cd may induce nephron atrophy, resulting in a reduction in the estimated glomerular filtration rate (eGFR) below 60 mL\/min\/1.73 m2. Herein, these pathologies were investigated in relation to Cd exposure, smoking, diabetes, and hypertension. The data were collected from 448 residents of Cd-polluted and non-polluted regions of Thailand. The body burden of Cd, indicated by the mean Cd excretion (ECd), normalized to creatinine clearance (Ccr) as (ECd\/Ccr) \u00d7 100 in women and men did not differ (3.21 vs. 3.12 \u00b5g\/L filtrate). After adjustment of the confounding factors, the prevalence odds ratio (POR) for tubulopathy and a reduced eGFR were increased by 1.9-fold and 3.2-fold for every 10-fold rise in the Cd body burden. In women only, a dose\u2013effect relationship was seen between \u03b22M excretion (E\u03b22M\/Ccr) and ECd\/Ccr (F = 3.431, \u03b72 0.021). In men, E\u03b22M\/Ccr was associated with diabetes (\u03b2 = 0.279). In both genders, the eGFR was inversely associated with E\u03b22M\/Ccr. The respective covariate-adjusted mean eGFR values were 16.5 and 12.3 mL\/min\/1.73 m2 lower in women and men who had severe tubulopathy ((E\u03b22M\/Ccr) \u00d7 100 \u2265 1000 \u00b5g\/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of E\u03b22M\/Ccr could be attributable mostly to Cd-induced impairment in the tubular reabsorption of the protein together with Cd-induced nephron loss, which is evident from an inverse relationship between E\u03b22M\/Ccr and the eGFR.<\/jats:p>","DOI":"10.3390\/toxics11070616","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:56:47Z","timestamp":1689555407000},"page":"616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Gender Differences in the Severity of Cadmium Nephropathy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-4227","authenticated-orcid":false,"given":"Supabhorn","family":"Yimthiang","sequence":"first","affiliation":[{"name":"Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-6650","authenticated-orcid":false,"given":"David A.","family":"Vesey","sequence":"additional","affiliation":[{"name":"The Centre for Kidney Disease Research, Translational Research Institute, Brisbane 4102, Australia"},{"name":"Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-7908","authenticated-orcid":false,"given":"Glenda C.","family":"Gobe","sequence":"additional","affiliation":[{"name":"The Centre for Kidney Disease Research, Translational Research Institute, Brisbane 4102, Australia"},{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia"},{"name":"NHMRC Centre of Research Excellence for CKD QLD, UQ Health Sciences, Royal Brisbane and Women\u2019s Hospital, Brisbane 4029, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phisit","family":"Pouyfung","sequence":"additional","affiliation":[{"name":"Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanaporn","family":"Khamphaya","sequence":"additional","affiliation":[{"name":"Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soisungwan","family":"Satarug","sequence":"additional","affiliation":[{"name":"The Centre for Kidney Disease Research, Translational Research Institute, Brisbane 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/00039890209602919","article-title":"Cadmium levels in the lung, liver, kidney cortex, and urine samples from Australians without occupational exposure to metals","volume":"57","author":"Satarug","year":"2002","journal-title":"Arch. Environ. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.envres.2009.10.010","article-title":"Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources","volume":"110","author":"Barregard","year":"2010","journal-title":"Environ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113119","DOI":"10.1016\/j.envres.2022.113119","article-title":"Low-level exposure to lead, cadmium and mercury, and histopathological findings in kidney biopsies","volume":"211","author":"Barregard","year":"2022","journal-title":"Environ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00204-022-03432-w","article-title":"Estimation of health risks associated with dietary cadmium exposure","volume":"97","author":"Satarug","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.14252\/foodsafetyfscj.D-22-00003","article-title":"Dietary exposure of the Japanese general population to elements: Total diet study 2013\u20132018","volume":"10","author":"Watanabe","year":"2022","journal-title":"Food Saf."},{"key":"ref_6","unstructured":"(2011). Summary and Conclusions, Proceedings of the Joint FAO\/WHO Expert Committee on Food Additives and Contaminants, Seventy-Third Meeting, Geneva, Switzerland, 8\u201317 June 2010, Food and Agriculture Organization of the United Nations\/World Health Organization. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/44521."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.5414\/CN110056","article-title":"A generic method for analysis of plasma concentrations","volume":"94","author":"Phelps","year":"2020","journal-title":"Clin. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1289\/ehp.1104769","article-title":"Modeling cadmium exposures in low- and high-exposure areas in Thailand","volume":"121","author":"Satarug","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yimthiang, S., Pouyfung, P., Khamphaya, T., Kuraeiad, S., Wongrith, P., Vesey, D.A., Gobe, G.C., and Satarug, S. (2022). Effects of environmental exposure to cadmium and lead on the risks of diabetes and kidney dysfunction. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19042259"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s10653-005-4670-7","article-title":"Heavy metals in soils and crops in Southeast Asia. 2. Thailand","volume":"26","author":"Zarcinas","year":"2004","journal-title":"Environ. Geochem. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/jch.12209","article-title":"Review of recent literature in hypertension: Updated clinical practice guidelines for chronic kidney disease now include albuminuria in the classification system","volume":"15","author":"Bloch","year":"2013","journal-title":"J. Clin. Hypertens"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1080\/1047322X.1990.10389587","article-title":"Estimation of average concentration in the presence of nondetectable values","volume":"5","author":"Hornung","year":"1990","journal-title":"Appl. Occup. Environ. Hyg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s12325-020-01568-8","article-title":"Burden of chronic kidney disease by KDIGO categories of glomerular filtration rate and albuminuria: A Systematic review","volume":"38","author":"Murton","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1053\/j.ajkd.2014.04.010","article-title":"Measuring GFR: A systematic review","volume":"64","author":"Soveri","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1001\/jama.2015.0602","article-title":"Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: A systematic review","volume":"313","author":"Levey","year":"2015","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1007\/s10653-019-00410-7","article-title":"Human health risk assessment of cadmium exposure through rice consumption in cadmium-contaminated areas of the Mae Tao sub-district, Tak, Thailand","volume":"42","author":"Suwatvitayakorn","year":"2020","journal-title":"Environ. Geochem. Health"},{"key":"ref_17","first-page":"133","article-title":"Human health effects from cadmium exposure: Comparison between persons living in cadmium-contaminated and non-contaminated areas in northwestern Thailand","volume":"46","author":"Swaddiwudhipong","year":"2015","journal-title":"Southeast Asian J. Trop. Med. Publ. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e3596","DOI":"10.1002\/dmrr.3596","article-title":"Role of renal tubular programed cell death in diabetic kidney disease","volume":"39","author":"Zhou","year":"2023","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"155195","DOI":"10.1016\/j.metabol.2022.155195","article-title":"Mitochondrial dysfunction in diabetic tubulopathy","volume":"131","author":"Yao","year":"2022","journal-title":"Metabolism"},{"key":"ref_20","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":"Madrigal","year":"2018","journal-title":"Environ. Res."},{"key":"ref_21","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":"Guallar","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ferraro, P.M., Costanzi, S., Naticchia, A., Sturniolo, A., and Gambaro, G. (2010). Low level exposure to cadmium increases the risk of chronic kidney disease: Analysis of the NHANES 1999\u20132006. BMC Public Health, 10.","DOI":"10.1186\/1471-2458-10-304"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.envres.2014.06.013","article-title":"Low serum zinc is associated with elevated risk of cadmium nephrotoxicity","volume":"134","author":"Lin","year":"2014","journal-title":"Environ. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fmed.2017.00073","article-title":"Rediscovering beta-2 microglobulin as a biomarker across the spectrum of kidney diseases","volume":"4","author":"Argyropoulos","year":"2017","journal-title":"Front. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/ki.1986.156","article-title":"Use of B2-microglobulin to diagnose tubulo-interstitial renal lesions in children","volume":"30","author":"Portman","year":"1986","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ki.1984.151","article-title":"Renal tubular absorption of beta 2 microglobulin","volume":"26","author":"Gauthier","year":"1984","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1172\/JCI106083","article-title":"Differentiation of glomerular, tubular, and normal proteinuria: Determination of urinary excretion of B2-microglobulin, albumin, and total protein","volume":"48","author":"Peterson","year":"1969","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Satarug, S., Vesey, D.A., Gobe, G.C., and \u0110or\u0111evi\u0107, A.B. (2022). The validity of benchmark dose limit analysis for estimating permissible accumulation of cadmium. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192315697"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.envres.2019.03.026","article-title":"The inverse association of glomerular function and urinary \u03b22-MG excretion and its implications for cadmium health risk assessment","volume":"173","author":"Satarug","year":"2019","journal-title":"Environ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/hr.2011.42","article-title":"Increases in urinary albumin and beta2-microglobulin are independently associated with blood pressure in the Japanese general population: The Takahata Study","volume":"34","author":"Mashima","year":"2011","journal-title":"Hypertens. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10157-010-0392-y","article-title":"The association between renal tubular damage and rapid renal deterioration in the Japanese population: The Takahata study","volume":"15","author":"Kudo","year":"2011","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1258\/136218004774202364","article-title":"Toxic metals and the menopause","volume":"10","author":"Vahter","year":"2004","journal-title":"J. Br. Menopause Soc."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/11\/7\/616\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:12:45Z","timestamp":1760127165000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/11\/7\/616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,15]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["toxics11070616"],"URL":"https:\/\/doi.org\/10.3390\/toxics11070616","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,15]]}}}