The NOAEL Equivalent of Environmental Cadmium Exposure Associated with GFR Reduction and Chronic Kidney Disease

与肾小球滤过率降低和慢性肾脏病相关的环境镉暴露的无观察到不良反应剂量当量

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Abstract

Cadmium (Cd) is a highly toxic metal pollutant present in virtually all food types. Health guidance values were established to safeguard against excessive dietary Cd exposure. The derivation of such health guidance figures has been shifted from the no-observed-adverse-effect level (NOAEL) to the lower 95% confidence bound of the benchmark dose (BMD), termed BMDL. Here, we used the PROAST software to calculate the BMDL figures for Cd excretion (E(Cd)) associated with a reduction in the estimated glomerular filtration rate (eGFR), and an increased prevalence of chronic kidney disease (CKD), defined as eGFR ≤ 60 mL/min/1.73 m(2). Data were from 1189 Thai subjects (493 males and 696 females) mean age of 43.2 years. The overall percentages of smokers, hypertension and CKD were 33.6%, 29.4% and 6.2%, respectively. The overall mean E(Cd) normalized to the excretion of creatinine (E(cr)) as E(Cd)/E(cr) was 0.64 µg/g creatinine. E(Cd)/E(cr), age and body mass index (BMI) were independently associated with increased prevalence odds ratios (POR) for CKD. BMI figures ≥24 kg/m(2) were associated with an increase in POR for CKD by 2.81-fold (p = 0.028). E(Cd)/E(cr) values of 0.38-2.49 µg/g creatinine were associated with an increase in POR for CKD risk by 6.2-fold (p = 0.001). The NOAEL equivalent figures of E(Cd)/E(cr) based on eGFR reduction in males, females and all subjects were 0.839, 0.849 and 0.828 µg/g creatinine, respectively. The BMDL/BMDU values of E(Cd)/E(cr) associated with a 10% increase in CKD prevalence were 2.77/5.06 µg/g creatinine. These data indicate that Cd-induced eGFR reduction occurs at relatively low body burdens and that the population health risk associated with E(Cd)/E(cr) of 2.77-5.06 µg/g creatinine was not negligible.

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