The association between dietary cadmium exposure and renal dysfunction – the benchmark dose estimation of reference levels: the ChinaCad study

Abstract

The tolerable dietary intake of cadmium was recommended at provisional tolerable monthly intake of 25 μg kg body weight. However, several studies indicated that this tolerable level should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using a benchmark dose (BMD) approach. A total of 790 subjects (302 men and 488 women) living in control and cadmium-polluted areas were included. The dietary cadmium intake was estimated by a food survey. Blood cadmium, urinary cadmium and renal function markers (microalbuminuria, N-acetyl-β-d-glucosaminidase [NAG] and its isoform B [NAGB], β -microglobulin and retinol binding protein) in urine were measured. We calculated the 95% lower confidence bounds of BMD (BMDLs) of cumulative cadmium intake. In control and two polluted areas, the median cumulative cadmium intake was 0.5, 2.1 and 11.1 g. The odds ratio of the intermediate (1.0-3.0 g), second highest (3.0-11.0 g) and the highest cumulative cadmium intake (>11.0 g) compared with the lowest cumulative cadmium intake (<1.0 g) were 2.8 (95% CI: 1.4-5.8), 8.1 (95% CI: 3.8-17.2) and 11.4 (95% CI: 6.5-26.4) for urinary NAG and 6.6 (95% CI: 3.2-13.8), 14.8 (95% CI: 6.8-32.2) and 22.5 (95% CI: 10.7-47.5) for urinary NAGB. The BMDLs of cumulative cadmium intake were 1.1-1.2 g (benchmark response [BMR] = 5%) for urinary NAG, and were 0.7-0.9 g (BMR = 5%) for urinary NAGB, and were 1.3-1.4 g (BMR = 5%) for urinary β -microglobulin. The BMDLs of cumulative cadmium intake in a Chinese population were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection.

Dose–response evaluation of urinary cadmium and kidney injury biomarkers in Chinese residents and dietary limit standards

“…For the high exposure sub-population with Cd exposure above the 95 th percentile, rice was still the main contributor (58.6%), followed by shellfish (13.2%) and leafy vegetables (9.2%) [ 38 ]. Another study in non-polluted areas of China pointed out that the median lifetime cumulative Cd intakes was 0.5 g [ 39 ], higher than the result from this study (0.37 g, calculated based on age 60). Due to the persistent of Cd in the environment and its high transfer rate from soil to plant [ 40 ], maintenance of low Cd in crops and leafy is pivotal.…”

Reply to T. Kawada: Cadmium exposure and renal effect

“…However, the estimation of BMD/BMDL values varied with populations, tubular indicators, cutoff values, or BMR being used. Literatures conducted in Japan or China also showed kind of gender difference in the BMD values(Chen et al, 2018;JECFA, 2011). Although JECFA has established the provisional tolerable monthly intake (PTWI) of 25 μg/kg body weight per month (0.83 μg/kg body weight/day or 58 μg/day for a 70-kg person) and a U-Cd threshold level of 5.24 μg/g creatinine based on the BMD/BMDL values of β2-MG and U-Cd (JECFA, 2011), studies frequently reported that kidney damage could occur with U-Cd lower than 5.24 μg/g creatinine.…”

The Beneficial Impact of Zinc Supplementation on the Vascular Tissue of the Abdominal Aorta under Repeated Intoxication with Cadmium: A Study in an In Vivo Experimental Model

“…The following are available online at , Table S1: The concentration of Cd in the blood and urine in particular experimental groups, Table S2: The concentration of Cd in the blood and urine of inhabitants of industrialized countries, Table S3: The concentration of Zn in the serum and urine in particular experimental groups, Figure S1: The effect of Zn administration on TAS, TOS, and OSI in the vascular tissue of the abdominal aorta of rats intoxicated with Cd, Figure S2: The effect of Zn administration on the concentrations of TC and TG in the vascular tissue of the abdominal aorta of rats intoxicated with Cd, Figure S3: The effect of Zn administration on the concentration of eNOS in the vascular tissue of the abdominal aorta of rats intoxicated with Cd, Figure S4: The effect of Zn administration on the concentrations of IL-1β and IL-10 in the vascular tissue of the abdominal aorta and the serum of rats intoxicated with Cd, Figure S5: The effect of Zn administration on the concentration of CRP in the serum of rats intoxicated with Cd, Figure S6: The effect of Zn administration on the concentration of VEGF in the serum of rats intoxicated with Cd, Figure S7: The effect of Zn administration on the expression of PECAM-1, ICAM-1, and L-selectin on the endothelial cells of the abdominal aorta of rats intoxicated with Cd, Figure S8: The effect of Zn administration on the expression of ICAM-1 and L-selectin on the leukocytes in the blood of rats intoxicated with Cd. Refs [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ] are cited in the Supplementary Materials.…”