Satarug Soisungwan, Vesey David A, Gobe Glenda C, Yimthiang Supabhorn, Buha Đorđević Aleksandra
Kidney Disease Research Collaborative, Translational Research Institute, Brisbane 4102, Australia.
Department of Nephrology, Princess Alexandra Hospital, Brisbane 4102, Australia.
Toxics. 2023 Jan 11;11(1):68. doi: 10.3390/toxics11010068.
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.
粮食作物尤其是大米中镉(Cd)含量的增加令人担忧,因为大米是世界上一半以上人口的主食。在一些地区,大米中的镉摄入量占总镉摄入量的50%以上。低环境镉暴露与白蛋白排泄增加至30 mg/g肌酐(称为白蛋白尿)以及估计肾小球滤过率(eGFR)逐渐降低至60 mL/min/1.73 m2以下(称为eGFR降低)有关。然而,关于高暴露条件下白蛋白尿的研究有限。在此,我们对镉污染地区和低暴露对照地区居民记录的相关数据进行了基准剂量(BMD)分析。我们将镉排泄率(ECd)和白蛋白排泄率(Ealb)相对于肌酐清除率(Ccr)进行标准化,得到ECd/Ccr和Ealb/Ccr,以校正各受试者存活肾单位数量的差异。我们首次确定了与临床相关的不良肾脏健康结局相关的镉排泄水平。Ealb/Ccr与ECd/Ccr(β = 0.239,p < 0.001)以及年龄(β = 0.203,p < 0.001)呈正相关,而血压正常与较低的Ealb/Ccr相关(β = -0.106,p = 0.009)。滤液中ECd/Ccr值在16.5至35.5 ng/L之间与10%的白蛋白尿患病率相关,而滤液中ECd/Ccr值为59 ng/L与10%的eGFR降低患病率相关。因此,白蛋白排泄增加和eGFR降低似乎在低身体负担时就会出现,它们应构成适用于计算食物链镉污染所致健康风险的毒性终点。