Use of Urinary β2-Microglobulin in the Assessment of the Health Risk from Environmental Cadmium Exposure

  1. Soisungwan Satarug
  2. David A. Vesey
  3. Aleksandra Buha Đorđević

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Abstract

Cadmium (Cd) is a ubiquitous environmental pollutant with no nutritional value or physiological role in the body. It readily accumulates in various tissues as it is easily absorbed from the diet but only poorly excreted. Due to the widespread contamination of staple foods, exposure to this toxic metal is inevitable for most people. The health risk due to dietary Cd exposure has long been underappreciated. This is primarily due to the use of urinary excretion of β2-microglobulin (β2M) as an indicator of an adverse health effect. This study employed advanced benchmark dose (BMD) modeling in a Thai cohort (n = 799) to reassess health risks from dietary Cd exposure. The BMD limit for urinary Cd was identified as 0.17 μg/g creatinine when using a reduction in estimated glomerular filtration rate (eGFR) as the endpoint, whereas no reliable BMD could be established using β2-microglobulin excretion. Given that eGFR reduction is a more reliable indicator of chronic kidney disease, its use is recommended for deriving health-protective guidelines. The findings demonstrate that the current urinary Cd threshold of 5.24 μg/g creatinine is inadequate, supporting the adoption of a threshold below 0.20 μg/g creatinine in future exposure guidelines.

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    Major issues

    • The study is tilted towards a cross sectional study rather than cohort analysis, because samples were collected just ones, and no longitudinal follow up of the participants. Excerpts from the manuscript supporting this claim are (Data on Cd excretion, β2M excretion and eGFR were from a Thai cohort of 799 persons. This is also supported by strategies used in the method section where samples of venous blood and morning voided urine were collected after an overnight fasting. 

    • In the method section, eGFR was calculated once. This reflects a misclassification as this reading has to last >/= 3months. Also, single spot urine sample introduces high variability because it varies with hydration and diet. Creatine correction also introduces bias because this doesn't fully reflect the true value of the result.

    • Recommendation (The BMD limit (BMDL) value for Cd excretion was 0.17 μg/g creatinine, when eGFR was used as an endpoint. In contrast, the BMDL for Cd excretion could not reliably be estimated, when β2M was used as an endpoint. Given that a reduced eGFR more reliably indicates the development of chronic kidney disease, we recommend the use of the eGFR to derive a meaningful health protective) doesn't match the study findings.

    Minor issues

    • The diagnostic criteria for CKD in the introductory section in my opinions is incorrect because, it should last for 3months and above and not at least 3months.

    • I am concerned about the reverse causality mentioned in the introduction not addressed in the study proper.

    • Adjustment was only made for age, BMI, gender, smoking and hypertension leaving occupational history, socio-economic status, NSAID use or other metals, which could also serve as confounders.

    • Results from figure 1c showed that women had higher BMDL than men but didn't discuss muscle creatine or its kinetics in the discussion section.

    Competing interests

    The authors declare that they have no competing interests.

    Use of Artificial Intelligence (AI)

    The authors declare that they did not use generative AI to come up with new ideas for their review.

  2. Version published to 10.3390/app152111757
  3. Version published to 10.20944/preprints202509.2442.v1