Is Urinary Cadmium a Biomarker of Long-term Exposure in Humans? A Review Original paper

What was reviewed?

This review examines urinary cadmium biomarker long-term exposure in humans and assesses how well urinary cadmium (U-Cd) reflects body burden over time. The authors explain cadmium toxicokinetics and show that kidneys store cadmium for decades and release small amounts into urine. They describe how U-Cd tracks renal cadmium and thus captures cumulative exposure better than blood cadmium in most non-occupational settings. They summarise evidence on factors that change U-Cd, such as smoking status, age, sex, iron status, renal physiology, and urine dilution. They also discuss analytical issues that can bias U-Cd, including creatinine normalisation and polyatomic interferences during ICP-MS analysis, and they propose ways to handle these issues in study design and interpretation.

Who was reviewed?

The review draws on adult populations from community cohorts and national surveys, plus residents of historically contaminated regions and some occupational groups. It includes never, former, and current smokers, and both men and women, with attention to women who have low iron stores and pregnancy history. It covers first-morning void, spot, and 24-hour urine sampling and compares their performance. It also pools data across studies to examine smoking strata by age and evaluates temporal stability using repeated measures in healthy participants. The authors give practical ranges for U-Cd in Western populations without unusual exposure and report how values differ when kidney disease or proteinuria changes renal handling.

Most important findings

U-Cd shows good to excellent temporal stability, with intraclass correlation coefficients between 0.66 and 0.81 across months to years and across spot and first-morning samples. This supports its use as a marker of long-term exposure rather than day-to-day intake. U-Cd rises with age and is higher in women, driven in part by lower iron stores that upregulate divalent metal transporters and increase cadmium absorption. Smoking exerts the strongest effect. Current smokers have the highest U-Cd, former smokers sit between current and never smokers, and differences persist decades after cessation, which reinforces U-Cd as an index of cumulative dose.

In Western general populations without unusual exposures, creatinine-normalised U-Cd usually stays below 2 μg/g. Creatinine normalisation corrects for urine dilution but can inflate age associations because creatinine falls with age; specific gravity offers an alternative. Kidney disease and proteinuria can increase U-Cd through co-excretion of cadmium-metallothionein, which risks reverse causality in cross-sectional links between U-Cd and renal outcomes. Analytical interferences during ICP-MS can bias low-level measurements unless laboratories manage isobaric and polyatomic overlaps. For microbiome studies, the paper does not report microbial taxa or community shifts; yet it supports U-Cd as a stable external exposure variable that investigators can align with gut or oral microbiome signatures, provided they stratify by smoking and account for iron status, sex, age, and renal function to avoid confounding.

Key implications

Clinicians and researchers can use U-Cd as a practical, stable marker of cumulative cadmium burden in population studies and translational work. They should stratify by smoking status, adjust for urine dilution, and record iron status, sex, and age in models. They should avoid over-interpreting cross-sectional associations with renal outcomes when proteinuria is present and should consider prospective designs. Microbiome researchers can pair U-Cd with host and microbial data as an exposure variable and include renal and iron measures to reduce bias. These steps improve risk estimates and make U-Cd more useful in both clinical and exposure–microbiome research.