Gender Differences in the Severity of Cadmium Nephropathy.

The excretion of β-microglobulin (βM) 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. 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), normalized to creatinine clearance (C) as (E/C) × 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 βM excretion (E/C) and E/C ( = 3.431, η 0.021). In men, E/C was associated with diabetes (β = 0.279). In both genders, the eGFR was inversely associated with E/C. The respective covariate-adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m lower in women and men who had severe tubulopathy ((E/C) × 100 ≥ 1000 µg/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of E/C 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/C and the eGFR.