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

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. The benchmark dose approach was applied to identify the thresholds of cadmium‐induced nephrotoxicity among 40‐75‐year‐old non‐smoking women in rural areas of southwest China, and results suggested that β2‐microglobulin and microalbumin in urine were good biomarkers for long‐term environmental Cd exposure assessment.