Gender Differences in the Severity of Cadmium Nephropathy.

The excretion of β 2 -microglobulin (β 2 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 2 . 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 Cd ), normalized to creatinine clearance (C cr ) as (E Cd /C cr ) × 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 2 M excretion (E β2M /C cr ) and E Cd /C cr ( F = 3.431, η 2 0.021). In men, E β2M /C cr was associated with diabetes (β = 0.279). In both genders, the eGFR was inversely associated with E β2M /C cr . The respective covariate-adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m 2 lower in women and men who had severe tubulopathy ((E β2M /C cr ) × 100 ≥ 1000 µg/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of E β2M /C cr 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 β2M /C cr and the eGFR.