Gender Differences in the Severity of Cadmium Nephropathy

The excretion of beta(2)-microglobulin (beta M-2) above 300 mu g/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 (ECd), normalized to creatinine clearance (C-cr) as (E-Cd/C-cr) x 100 in women and men did not differ (3.21 vs. 3.12 mu g/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 beta M-2 excretion (E beta M-2/C-cr) and E-Cd/C-cr (F = 3.431, eta(2) 0.021). In men, E-beta 2M/C-cr was associated with diabetes (beta = 0.279). In both genders, the eGFR was inversely associated with E-beta 2M/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-beta 2M/C-cr) x 100 >= 1000 mu g/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of E-beta 2M/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-beta 2M/C-cr and the eGFR.

Automated summary

The study investigated the relationship between cadmium exposure and renal pathologies in residents of Cd-polluted and non-polluted regions in Thailand. It was found that chronic cadmium exposure was associated with tubulopathy and a reduced estimated glomerular filtration rate (eGFR), particularly in women. The study also revealed that cadmium-induced impairment in protein reabsorption and nephron loss contributed to the increase in tubulopathy.