| Summary: | 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.
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