Article
Version 1
Preserved in Portico This version is not peer-reviewed
Gender Differences in the Severity of Cadmium Nephropathy
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Version 1
: Received: 28 June 2023 / Approved: 29 June 2023 / Online: 29 June 2023 (07:23:56 CEST)
A peer-reviewed article of this Preprint also exists.
Yimthiang, S.; Vesey, D.A.; Gobe, G.C.; Pouyfung, P.; Khamphaya, T.; Satarug, S. Gender Differences in the Severity of Cadmium Nephropathy. Toxics 2023, 11, 616. Yimthiang, S.; Vesey, D.A.; Gobe, G.C.; Pouyfung, P.; Khamphaya, T.; Satarug, S. Gender Differences in the Severity of Cadmium Nephropathy. Toxics 2023, 11, 616.
Abstract
Excretion of β2-microglobulin (β2M) 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 m2. Herein, these pathologies were investigated in relation to Cd exposure, smoking, diabetes and hypertension. Data were 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 (Ccr) as (ECd/Ccr) ×100 in women and men did not differ (3.21 vs. 3.12 µg/L filtrate). 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 Cd body burden. In women only, a dose-effect relationship was seen between β2M excretion (Eβ2M/Ccr) and ECd/Ccr (F = 3.431, η2 0.021). In men, Eβ2M/Ccr was associated with diabetes (β = 0.279). In both genders, eGFR was inversely associated with Eβ2M/Ccr. The respective covariate- adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m2 lower in women and men who had severe tubulopathy; (Eβ2M/Ccr) ×100 ≥ 1000 µg/L filtrate. These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of Eβ2M/Ccr could be attributable mostly to Cd-induced impairment in tubular reabsorption of the protein together with Cd-induced nephron loss, evident from an inverse relationship between Eβ2M/Ccr and the eGFR.
Keywords
β2-microglobulin; cadmium; diabetes; GFR; hypertension; smoking; tubular proteinuria
Subject
Public Health and Healthcare, Public, Environmental and Occupational Health
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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