{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:16:47Z","timestamp":1789139807606,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>We retrospectively analyzed data on the excretion of cadmium (ECd), \u03b22-microglobulin (E\u03b22M) and N-acetyl-\u03b2-D-glucosaminidase (ENAG), which were recorded for 734 participants in a study conducted in low- and high-exposure areas of Thailand. Increased E\u03b22M and ENAG were used to assess tubular integrity, while a reduction in the estimated glomerular filtration rate (eGFR) was a criterion for glomerular dysfunction. ECd, E\u03b22M and ENAG were normalized to creatinine clearance (Ccr) as ECd\/Ccr, E\u03b22M\/Ccr and ENAG\/Ccr to correct for interindividual variation in the number of surviving nephrons and to eliminate the variation in the excretion of creatinine (Ecr). For a comparison, these parameters were also normalized to Ecr as ECd\/Ecr, E\u03b22M\/Ecr and ENAG\/Ecr. According to the covariance analysis, a Cd-dose-dependent reduction in eGFR was statistically significant only when Ecd was normalized to Ccr as ECd\/Ccr (F = 11.2, p &lt; 0.001). There was a 23-fold increase in the risk of eGFR \u2264 60 mL\/min\/1.73 m2 in those with the highest ECd\/Ccr range (p = 0.002). In addition, doubling of ECd\/Ccr was associated with lower eGFR (\u03b2 = \u22120.300, p &lt; 0.001), and higher ENAG\/Ccr (\u03b2 = 0.455, p &lt; 0.001) and E\u03b22M\/Ccr (\u03b2 = 0.540, p &lt; 0.001). In contrast, a covariance analysis showed a non-statistically significant relationship between ECd\/Ecr and eGFR (F = 1.08, p = 0.165), while the risk of low eGFR was increased by 6.9-fold only among those with the highest ECd\/Ecr range. Doubling of ECd\/Ecr was associated with lower eGFR and higher ENAG\/Ecr and E\u03b22M\/Ecr, with the \u03b2 coefficients being smaller than in the Ccr-normalized dataset. Thus, normalization of Cd excretion to Ccr unravels the adverse effect of Cd on GFR and provides a more accurate evaluation of the severity of the tubulo-glomerular effect of Cd.<\/jats:p>","DOI":"10.3390\/ijerph191710572","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T21:28:12Z","timestamp":1661462892000},"page":"10572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dose\u2013Response Analysis of the Tubular and Glomerular Effects of Chronic Exposure to Environmental Cadmium"],"prefix":"10.3390","volume":"19","author":[{"given":"Soisungwan","family":"Satarug","sequence":"first","affiliation":[{"name":"Kidney Disease Research Collaborative, Translational Research Institute, Brisbane 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-6650","authenticated-orcid":false,"given":"David A.","family":"Vesey","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Princess Alexandra Hospital, Brisbane 4075, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-7908","authenticated-orcid":false,"given":"Glenda C.","family":"Gobe","sequence":"additional","affiliation":[{"name":"Kidney Disease Research Collaborative, 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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nordberg, M., and Nordberg, G.F. 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