Health Risk in a Geographic Area of Thailand with Endemic Cadmium Contamination: Focus on Albuminuria

Abstract

An increased level of cadmium (Cd) in food crops, especially rice is concerning because rice is a staple food for over half of the world’s population. In some regions, rice contributes to more than 50% of the total Cd intake. Low environmental exposure to Cd has been linked to an increase in albumin excretion to 30 mg/g creatinine, termed albuminuria, and a progressive reduction in the estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73 m2, termed reduced eGFR. However, research into albuminuria in high exposure conditions is limited. Here, we applied benchmark dose (BMD) analysis to the relevant data recorded for the residents of a Cd contamination area and a low-exposure control area. We normalized the excretion rates of Cd (ECd) and albumin (Ealb) to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr to correct for differences among subjects in the number of surviving nephrons. For the first time, we defined the excretion levels of Cd associated with clinically relevant adverse kidney health outcomes. Ealb/Ccr varied directly with ECd/Ccr (β = 0.239, p < 0.001), and age (β = 0.203, p < 0.001), while normotension was associated with lower Ealb/Ccr (β = −0.106, p = 0.009). ECd/Ccr values between 16.5 and 35.5 ng/L of the filtrate were associated with a 10% prevalence of albuminuria, while the ECd/Ccr value of 59 ng/L of the filtrate was associated with a 10% prevalence of reduced eGFR. Thus, increased albumin excretion and eGFR reduction appeared to occur at low body burdens, and they should form toxicity endpoints suitable for the calculation of health risk due to the Cd contamination of food chains.

The pathogenesis of albuminuria in cadmium nephropathy

“…We assembled archived data from 519 citizens of Thailand who resided in Cd-contaminated areas of Mae Sot District, Tak Province ( Satarug et al, 2013 , Satarug et al, 2023a ). Excessive levels of Cd were documented in soil samples and rice ( Suwatvitayakorn et al, 2020 ).…”

Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

“…Nearly all studies used ACR to define albuminuria and urinary Cd normalised to E cr as E Cd /E cr to indicate long-term exposure to Cd. However, the E cr -adjustment appeared to introduce variance to datasets, which created a high degree of statistical uncertainty [23]. In effect, the associations between E Cd /E cr and eGFR and E alb /E cr (ACR) are statistically insignificant (Section 2.3).…”

Modulation of the Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters

“…When GFR loss was used as a toxic endpoint, the NOAEL equivalent value or a toxicity threshold level of urinary Cd excretion ranged between 0.01 and 0.02 µg/g creatinine [39,52], which is at least 250 times less than 5.24 µg/g creatinine used by the JECFA to derive a tolerable intake level for Cd [38]. There is no safe level of Cd exposure.…”