{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:43:58Z","timestamp":1760060638724,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Walailak University, Nakhon Si Thammarat Province, Thailand","award":["WU-IRG-63-026"],"award-info":[{"award-number":["WU-IRG-63-026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Elevated levels of circulating \u03b22-microglobulin (\u03b22M) are linked to an increased risk of hypertension and mortality from diabetes. The present study tests the hypothesis that the environmental pollutants, cadmium (Cd) and lead (Pb), by increasing plasma \u03b22M levels, promote the development of hypertension and progression of diabetic kidney disease. Herein, we analyzed data from a Thai cohort of 72 individuals with diabetes and 65 controls without diabetes who were chronically exposed to low levels of Cd and Pb. In all subjects, serum concentrations of \u03b22M inversely correlated with the estimated glomerular filtration rate (eGFR) (r = \u22120.265) and directly with age (r = 0.200), fasting plasma glucose (r = 0.210), and systolic blood pressure (r = 0.229). The prevalence odds ratio (POR) for hyperglycemia increased 7.7% for every 1-year increase in age and increased 3.9-fold, 3.1-fold, and 3.7-fold in those with serum \u03b22M levels \u2265 5 mg\/L, Cd\/Pb exposure categories 2 and 3, respectively. The POR for hypertension increased 2.9-fold, 3-fold, and 4-fold by hyperglycemia (p = 0.011), Cd\/Pb exposure categories 2 and 3. The POR for albuminuria increased 3.5-fold by hyperglycemia. In conclusion, kidney damage, evident from albuminuria, was particularly pronounced in participants with diabetes who had a serum \u03b22M above 5 mg\/L plus chronic exposure to low-dose Cd and Pb. For the first time, through a mediation analysis, we provide evidence that links Cd exposure to the SH2B3-\u03b22M pathway of blood pressure homeostasis in people with and without diabetes.<\/jats:p>","DOI":"10.3390\/ijms26189208","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:04:44Z","timestamp":1758546284000},"page":"9208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Kidney Damage in Individuals with Diabetes Who Are Chronically Exposed to Cadmium and Lead: The Emergent Role for \u03b22-Microglobulin"],"prefix":"10.3390","volume":"26","author":[{"given":"Soisungwan","family":"Satarug","sequence":"first","affiliation":[{"name":"Centre for Kidney Disease Research, Translational Research Institute, Woolloongabba, Brisbane, QLD 4102, Australia"}],"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":"Centre for Kidney Disease Research, Translational Research Institute, Woolloongabba, Brisbane, QLD 4102, Australia"},{"name":"Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donrawee","family":"Waeyeng","sequence":"additional","affiliation":[{"name":"Environmental Health and Technology, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-4227","authenticated-orcid":false,"given":"Supabhorn","family":"Yimthiang","sequence":"additional","affiliation":[{"name":"Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1161\/HYPERTENSIONAHA.120.15026","article-title":"2020 International Society of Hypertension Global Hyperten-sion Practice Guidelines","volume":"75","author":"Unger","year":"2020","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/S0140-6736(20)30752-2","article-title":"Global burden of 87 risk factors in 204 countries and territories, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Murray","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1161\/HYPERTENSIONAHA.108.189141","article-title":"Resistant hypertension: Diagnosis, evaluation, and treatment. 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