What threshold of urinary cadmium (Cd-U) is currently considered indicative of early renal tubular dysfunction in exposed adult populations?
I am conducting a study on chronic environmental cadmium exposure and its nephrotoxic effects, particularly focusing on early biomarkers of renal tubular damage. Several sources suggest 2 µg/g creatinine as a reference point, but variability exists depending on population, sex, and co-exposure.
Could experts clarify which threshold (e.g. 1 µg/g, 2 µg/g, or 5 µg/g creatinine) is most reliable or currently used in risk assessments and clinical practice?
Could experts clarify which threshold (e.g. 1 µg/g, 2 µg/g, or 5 µg/g creatinine) is most reliable or currently used in risk assessments and clinical practice?
3 Answers
KFC
Cd is a chemical element that is both genotoxic and carcinogenic at high concentrations in the human body. It is classified by the International Agency for Research on Cancer as potential, in Group I carcinogen (IARC, 1993, 2012). Cd has physical and chemical properties similar to those of zinc and calcium, enabling it to pass easily through biological tissues. In solutions, in the absence of organic ligands, its most common forms are Cd2+, CdSO40, CdCl+ and CdHCO3+ (IRSN, 2004). In air, it is often in particulate, oxide, sulfide or chloride form (IARC, 2012; WHO, 2000). Cd enters the human body via metabolic pathways through ingestion of food, drinking water, tobacco consumption or inhalation of contaminated air. Once present in the human body, it is mainly found in erythrocytes via metallothioneins (IARC, 1993). The United States Environmental Protection Agency (USEPA, 2002) has estimated a cancer risk index (CR) of between 1E-06 and 1E-04.)
For kidney function, blood creatinine and glomerular filtration rate (GFR) are often monitored. However, according to the work of Levey, A. S et al. (2003), blood creatinine is estimated at 1.2 mg/dL in adult men or 1.1 mg/dL in women; and a GFR of less than 60 mL/min/1.73 m2 indicates chronic renal failure.
The threshold for renal toxicity associated with certain drugs, such as aminoglycosides or chiotherapy, is often related to plasma concentration or cumulative dose. For example, a peak plasma concentration above 2 mg/L for gentamicin may increase the risk of nephrotoxicity (Matzke, G. R et al., 2009).
For kidney function, blood creatinine and glomerular filtration rate (GFR) are often monitored. However, according to the work of Levey, A. S et al. (2003), blood creatinine is estimated at 1.2 mg/dL in adult men or 1.1 mg/dL in women; and a GFR of less than 60 mL/min/1.73 m2 indicates chronic renal failure.
The threshold for renal toxicity associated with certain drugs, such as aminoglycosides or chiotherapy, is often related to plasma concentration or cumulative dose. For example, a peak plasma concentration above 2 mg/L for gentamicin may increase the risk of nephrotoxicity (Matzke, G. R et al., 2009).
Arvind
This study provides the first evidence that a clinical measure of kidney function, specifically estimated glomerular filtration rates, can be directly associated with cadmium (Cd) exposure and resultant tubular toxicity in a manner dependent on both the dose and severity of toxicity. They have identified that a urinary Cd concentration as low as 0.50 μg/g creatinine may serve as an early warning indicator for excessive Cd intake, toxic burden, the onset of renal pathology, and progressive decline in kidney function. This threshold is particularly significant as it is ten times lower than the current FAO/WHO benchmark for kidney toxicity, which stands at 5.24 μg/g creatinine. This data strongly suggest that this established urinary Cd limit fails to provide adequate protection for public health. Therefore, there is a compelling and immediate need to re-evaluate both the Cd toxicity burden and the urinary Cd threshold for toxicity, ensuring that revised standards more effectively safeguard populations from excessive Cd exposure and the subsequent risk of developing chronic kidney disease.
Whereas the commonly seen limit in various literature is 2 µg/g creatinine, which is quite high.