Gender Differences in the Severity of Cadmium Nephropathy
The excretion of β<sub>2</sub>-microglobulin (β<sub>2</sub>M) above 300 µg/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, res...
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MDPI AG
2023-07-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/7/616 |
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| author | Supabhorn Yimthiang David A. Vesey Glenda C. Gobe Phisit Pouyfung Tanaporn Khamphaya Soisungwan Satarug |
| author_facet | Supabhorn Yimthiang David A. Vesey Glenda C. Gobe Phisit Pouyfung Tanaporn Khamphaya Soisungwan Satarug |
| author_sort | Supabhorn Yimthiang |
| collection | DOAJ |
| description | The excretion of β<sub>2</sub>-microglobulin (β<sub>2</sub>M) above 300 µg/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 m<sup>2</sup>. 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 (E<sub>Cd</sub>), normalized to creatinine clearance (C<sub>cr</sub>) as (E<sub>Cd</sub>/C<sub>cr</sub>) × 100 in women and men did not differ (3.21 vs. 3.12 µg/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–effect relationship was seen between β<sub>2</sub>M excretion (E<sub>β2M</sub>/C<sub>cr</sub>) and E<sub>Cd</sub>/C<sub>cr</sub> (<i>F</i> = 3.431, η<sup>2</sup> 0.021). In men, E<sub>β2M</sub>/C<sub>cr</sub> was associated with diabetes (β = 0.279). In both genders, the eGFR was inversely associated with E<sub>β2M</sub>/C<sub>cr</sub>. The respective covariate-adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m<sup>2</sup> lower in women and men who had severe tubulopathy ((E<sub>β2M</sub>/C<sub>cr</sub>) × 100 ≥ 1000 µg/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of E<sub>β2M</sub>/C<sub>cr</sub> 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<sub>β2M</sub>/C<sub>cr</sub> and the eGFR. |
| first_indexed | 2024-03-11T00:35:23Z |
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| last_indexed | 2024-03-11T00:35:23Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-94aeedf247af46faaae4cdb47b7ff84c2023-11-18T21:37:23ZengMDPI AGToxics2305-63042023-07-0111761610.3390/toxics11070616Gender Differences in the Severity of Cadmium NephropathySupabhorn Yimthiang0David A. Vesey1Glenda C. Gobe2Phisit Pouyfung3Tanaporn Khamphaya4Soisungwan Satarug5Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, ThailandThe Centre for Kidney Disease Research, Translational Research Institute, Brisbane 4102, AustraliaThe Centre for Kidney Disease Research, Translational Research Institute, Brisbane 4102, AustraliaOccupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, ThailandOccupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, ThailandThe Centre for Kidney Disease Research, Translational Research Institute, Brisbane 4102, AustraliaThe excretion of β<sub>2</sub>-microglobulin (β<sub>2</sub>M) above 300 µg/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 m<sup>2</sup>. 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 (E<sub>Cd</sub>), normalized to creatinine clearance (C<sub>cr</sub>) as (E<sub>Cd</sub>/C<sub>cr</sub>) × 100 in women and men did not differ (3.21 vs. 3.12 µg/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–effect relationship was seen between β<sub>2</sub>M excretion (E<sub>β2M</sub>/C<sub>cr</sub>) and E<sub>Cd</sub>/C<sub>cr</sub> (<i>F</i> = 3.431, η<sup>2</sup> 0.021). In men, E<sub>β2M</sub>/C<sub>cr</sub> was associated with diabetes (β = 0.279). In both genders, the eGFR was inversely associated with E<sub>β2M</sub>/C<sub>cr</sub>. The respective covariate-adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m<sup>2</sup> lower in women and men who had severe tubulopathy ((E<sub>β2M</sub>/C<sub>cr</sub>) × 100 ≥ 1000 µg/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of E<sub>β2M</sub>/C<sub>cr</sub> 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<sub>β2M</sub>/C<sub>cr</sub> and the eGFR.https://www.mdpi.com/2305-6304/11/7/616β<sub>2</sub>-microglobulincadmiumdiabetesGFRhypertensionsmoking |
| spellingShingle | Supabhorn Yimthiang David A. Vesey Glenda C. Gobe Phisit Pouyfung Tanaporn Khamphaya Soisungwan Satarug Gender Differences in the Severity of Cadmium Nephropathy Toxics β<sub>2</sub>-microglobulin cadmium diabetes GFR hypertension smoking |
| title | Gender Differences in the Severity of Cadmium Nephropathy |
| title_full | Gender Differences in the Severity of Cadmium Nephropathy |
| title_fullStr | Gender Differences in the Severity of Cadmium Nephropathy |
| title_full_unstemmed | Gender Differences in the Severity of Cadmium Nephropathy |
| title_short | Gender Differences in the Severity of Cadmium Nephropathy |
| title_sort | gender differences in the severity of cadmium nephropathy |
| topic | β<sub>2</sub>-microglobulin cadmium diabetes GFR hypertension smoking |
| url | https://www.mdpi.com/2305-6304/11/7/616 |
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