Associations between Urinary Excretion of Cadmium and Renal Biomarkers in Nonsmoking Females: A Cross-Sectional Study in Rural Areas of South China

Zhang, Yun-rui; Wang, Ping; Liang, Xiaoyan; Tan, Chuen Seng; Tan, Jianbin; Wang, Jing; Huang, Qiong; Huang, Rui; Li, Zhixue; Wen-cai, Chen; Wu, Shuqi; Ong, Choon Nam; Yang, Xingfen; Wu, Yongning

doi:10.3390/ijerph121011988

Cited by 30 publications

(20 citation statements)

References 40 publications

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“…Consistently, the result of our study suggested that MT was correlated with U-Cd but not B-Cd, which was similar to the study conducted by Roels et al (Roels et al, 1983). Further studies conducted among different populations exposed to environmental Cd have also confirmed the strong association between Cd and MT in urine (Kawada, Tohyama, & Suzuki, 1990;Zhang et al, 2015). These observations show the importance of MT in the renal excretion of Cd and are reminiscent of associations found in our study between U-Cd and α 1 -MG or RBP.…”

Section: Discussionsupporting

confidence: 88%

Benchmark dose estimation of urinary and blood cadmium as biomarkers of renal dysfunction among 40‐75‐year‐old non‐smoking women in rural areas of southwest China

Yan

Huo

et al. 2019

J of Applied Toxicology

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This study evaluated the association between urinary cadmium (U‐Cd) and blood Cd (B‐Cd) and several biomarkers of renal dysfunction (α1‐microglobulin [α1‐MG], β2‐microglobulin [β2‐MG], N‐acetyl‐β‐d‐glucosaminidase, metallothionein, retinol‐binding protein and microalbumin [mALB]) and identified the biomarker(s) that was most closely correlated with U‐Cd and B‐Cd among female residents in rural areas of southwest China. U‐Cd, creatinine (Cr), B‐Cd and the above‐mentioned six biomarkers in morning spot urine samples were measured from 288 randomly selected 40‐75‐year‐old non‐smoking women from non‐polluted areas and Cd‐polluted‐areas. The lower 95% confidence limit of the benchmark dose (BMD) corresponding to the 5% (BMDL05) and 10% benchmark response (BMDL10) was calculated with assumed cut‐off values of the 95th and 90th percentile. Among the investigated women, a significant positive association was found among mALB, β2‐MG and U‐Cd as well as B‐Cd. By using the cut‐off value of the 95th percentile, the BMDL05/BMDL10 of U‐Cd and B‐Cd were 4.33/8.89 μg/g Cr for mALB and 1.35/2.77 μg/L for β2‐MG, respectively. The BMDL05/BMDL10 of U‐Cd (B‐Cd) was 2.73/5.60 μg/g Cr (1.00/2.05 μg/L) for mALB, if the cut‐off value was set at the 90th percentile. Therefore, β2‐MG and mALB in urine were good biomarkers for long‐term environmental Cd exposure assessment among the six biomarkers studied for the study pool in southwest China. Our findings may help us to understand the association between nephrotoxicity and Cd exposure, and aid in the decision‐making of authorities for environmental Cd pollution and public health.

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Section: Discussionsupporting

confidence: 88%

Benchmark dose estimation of urinary and blood cadmium as biomarkers of renal dysfunction among 40‐75‐year‐old non‐smoking women in rural areas of southwest China

Yan

Huo

et al. 2019

J of Applied Toxicology

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“…Other investigators have described direct relationships of [NAG] u /[cr] u and eGFR to [Cd] u /[cr] u , but we have not found a synthesis of those relationships into a satisfactory pathophysiologic narrative [35,[43][44][45][46][47][48]. A cogent interpretation of Figures 1-3 must explain how eGFR and E NAG /C cr -results of cumulative Cd sequestration-were related physiologically to E Cd /C cr , an indicator of Cd excretion at the time of sampling.…”

Section: Discussionmentioning

confidence: 76%

The Source and Pathophysiologic Significance of Excreted Cadmium

Satarug

Vesey

Ruangyuttikarn

et al. 2019

Toxics

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In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd]u); N-acetyl-β-d-glucosaminidase, a marker of cellular damage ([NAG]u); and β2-microglobulin, an indicator of reabsorptive dysfunction ([β2MG]u). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (ECd/Ccr, ENAG/Ccr, and Eβ2MG/Ccr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on ECd/Ccr, eGFR on ENAG/Ccr, and ENAG/Ccr on ECd/Ccr. Estimated GFR varied inversely with both ratios, and ENAG/Ccr varied directly with ECd/Ccr. Linear and quadratic regressions of Eβ2MG/Ccr on ECd/Ccr and ENAG/Ccr were significant in moderate and high Cd-exposure groups. The association of ENAG/Ccr with ECd/Ccr implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that ECd/Ccr, ENAG/Ccr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd.

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“…In the later stages of Cd-induced renal injury, the tubular epithelial cells may shrink, fall off, and even disappear, and the tissue source of UNAG is lost [46]. The reabsorption function of the kidney is impaired when UNAG was released, and the excretion of Uβ 2 -MG may be greater than that of UNAG [47,48], which may be why Uβ 2 -MG produces higher values than UNAG in biological monitoring. In addition, the correlation coefficients for Uβ 2 -MG affecting UCd were higher than those for UNAG (Table 4).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that the accumulation and excretion of UNAG and Uβ 2 -MG increases significantly with the increase of Cd burden in the organism, and irreversible kidney damage becomes more serious as Cd exposure grows [48,50].…”

Section: Discussionmentioning

confidence: 99%