Environmental metal exposures and kidney function of Guatemalan sugarcane workers

Butler-Dawson, Jaime; James, Katherine A.; Krisher, Lyndsay; Jaramillo, Diana; Dally, Miranda; Neumann, Natalie; Pilloni, Daniel; Cruz, Alex; Asensio, Claudia Mariana; Johnson, Richard J.; Adgate, John L.; Newman, Lee S.

doi:10.1038/s41370-021-00292-x

Cited by 29 publications

(21 citation statements)

References 45 publications

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“…An upward trend of its incidence continues, while an adverse effect of Cd on eGFR and the risk of CKD have increasingly been reported. Higher Cd excretion was associated with lower eGFR in studies from Guatemala [ 54 ] and Myanmar [ 55 ]. The effect of Cd exposure on eGFR observed in children is particularly concerning.…”

Section: Discussionmentioning

confidence: 99%

The NOAEL Equivalent of Environmental Cadmium Exposure Associated with GFR Reduction and Chronic Kidney Disease

Satarug

Djordjevic

Yimthiang

et al. 2022

Toxics

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Cadmium (Cd) is a highly toxic metal pollutant present in virtually all food types. Health guidance values were established to safeguard against excessive dietary Cd exposure. The derivation of such health guidance figures has been shifted from the no-observed-adverse-effect level (NOAEL) to the lower 95% confidence bound of the benchmark dose (BMD), termed BMDL. Here, we used the PROAST software to calculate the BMDL figures for Cd excretion (ECd) associated with a reduction in the estimated glomerular filtration rate (eGFR), and an increased prevalence of chronic kidney disease (CKD), defined as eGFR ≤ 60 mL/min/1.73m2. Data were from 1189 Thai subjects (493 males and 696 females) mean age of 43.2 years. The overall percentages of smokers, hypertension and CKD were 33.6%, 29.4% and 6.2%, respectively. The overall mean ECd normalized to the excretion of creatinine (Ecr) as ECd/Ecr was 0.64 µg/g creatinine. ECd/Ecr, age and body mass index (BMI) were independently associated with increased prevalence odds ratios (POR) for CKD. BMI figures ≥ 24 kg/m2 were associated with an increase in POR for CKD by 2.81-fold (p = 0.028). ECd/Ecr values of 0.38−2.49 µg/g creatinine were associated with an increase in POR for CKD risk by 6.2-fold (p = 0.001). The NOAEL equivalent figures of ECd/Ecr based on eGFR reduction in males, females and all subjects were 0.839, 0.849 and 0.828 µg/g creatinine, respectively. The BMDL/BMDU values of ECd/Ecr associated with a 10% increase in CKD prevalence were 2.77/5.06 µg/g creatinine. These data indicate that Cd-induced eGFR reduction occurs at relatively low body burdens and that the population health risk associated with ECd/Ecr of 2.77−5.06 µg/g creatinine was not negligible.

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Section: Discussionmentioning

confidence: 99%

The NOAEL Equivalent of Environmental Cadmium Exposure Associated with GFR Reduction and Chronic Kidney Disease

Satarug

Djordjevic

Yimthiang

et al. 2022

Toxics

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“…Inflammation and fibrosis follow, nephrons are lost, and the GFR falls [ 19 ]. In a recent histopathological examination of kidney biopsies from healthy kidney transplant donors [ 29 ], the degree of tubular atrophy was positively associated with the level of Cd accumulation. Tubular atrophy was observed at relatively low Cd levels (median: 13 µg/g wet tissue weight) [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Dose–Response Analysis of the Tubular and Glomerular Effects of Chronic Exposure to Environmental Cadmium

Satarug

Vesey

Gobé

2022

IJERPH

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We retrospectively analyzed data on the excretion of cadmium (ECd), β2-microglobulin (Eβ2M) and N-acetyl-β-D-glucosaminidase (ENAG), which were recorded for 734 participants in a study conducted in low- and high-exposure areas of Thailand. Increased Eβ2M and ENAG were used to assess tubular integrity, while a reduction in the estimated glomerular filtration rate (eGFR) was a criterion for glomerular dysfunction. ECd, Eβ2M and ENAG were normalized to creatinine clearance (Ccr) as ECd/Ccr, Eβ2M/Ccr and ENAG/Ccr to correct for interindividual variation in the number of surviving nephrons and to eliminate the variation in the excretion of creatinine (Ecr). For a comparison, these parameters were also normalized to Ecr as ECd/Ecr, Eβ2M/Ecr and ENAG/Ecr. According to the covariance analysis, a Cd-dose-dependent reduction in eGFR was statistically significant only when Ecd was normalized to Ccr as ECd/Ccr (F = 11.2, p < 0.001). There was a 23-fold increase in the risk of eGFR ≤ 60 mL/min/1.73 m2 in those with the highest ECd/Ccr range (p = 0.002). In addition, doubling of ECd/Ccr was associated with lower eGFR (β = −0.300, p < 0.001), and higher ENAG/Ccr (β = 0.455, p < 0.001) and Eβ2M/Ccr (β = 0.540, p < 0.001). In contrast, a covariance analysis showed a non-statistically significant relationship between ECd/Ecr and eGFR (F = 1.08, p = 0.165), while the risk of low eGFR was increased by 6.9-fold only among those with the highest ECd/Ecr range. Doubling of ECd/Ecr was associated with lower eGFR and higher ENAG/Ecr and Eβ2M/Ecr, with the β coefficients being smaller than in the Ccr-normalized dataset. Thus, normalization of Cd excretion to Ccr unravels the adverse effect of Cd on GFR and provides a more accurate evaluation of the severity of the tubulo-glomerular effect of Cd.

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“…In other words, people with pre-existing chronic diseases are more vulnerable to high levels of Cd exposure, and they were at high risk of exposure to Cd and its potential adverse health effects. Chronic exposure to lower levels of Cd can accumulate in kidneys, and may induce kidney disease, and adverse hepatic and bone health [24]. Cd exposure can relate to early signs of renal damage, proteinuria, calcium loss, and tubular lesion [25].…”

Section: Discussionmentioning

confidence: 99%

Trends in Urinary and Blood Cadmium Levels in U.S. Adults with or without Comorbidities, 1999–2018

Yang

2022

Nutrients

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Although cadmium (Cd) exposure has been declining in the United States (U.S.) over the years, the level of exposure for people with pre-existing comorbidities is unclear. This study characterized the trends of blood Cd levels (bCd) (n = 44,498) and urinary Cd levels (uCd) (n = 15,107) by pre-existing comorbidities among adults participating in the U.S. National Health and Nutrition Examination Survey. We calculated age- and sex-standardized annual geometric mean (GM) levels, and used aJoinpoint regression model to examine the trends over time. The GM levels of bCd declined from 1999–2000 to 2017–2018 survey cycles (from 0.49 to 0.33 μg/L), while women and current smokers had higher levels. Participants with comorbidities had higher bCd and declined over time: cardiovascular disease (CVD) (0.50 to 0.42 μg/L), hypertension (0.49 to 0.35 μg/L), chronic kidney disease (CKD) (0.54 to 0.37 μg), and cancer (0.57 to 0.38 μg) versus those without these comorbidities. We observed the similar pattern of changes for uCd and participants with CVD, CKD, and cancer had higher levels. To conclude, the trend in urinary and blood Cd levels in U.S adults decreased in the past 20 years, and the levels varied by sex, smoking status, and comorbidities.

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Environmental metal exposures and kidney function of Guatemalan sugarcane workers

Cited by 29 publications

References 45 publications

The NOAEL Equivalent of Environmental Cadmium Exposure Associated with GFR Reduction and Chronic Kidney Disease

The NOAEL Equivalent of Environmental Cadmium Exposure Associated with GFR Reduction and Chronic Kidney Disease

Dose–Response Analysis of the Tubular and Glomerular Effects of Chronic Exposure to Environmental Cadmium

Trends in Urinary and Blood Cadmium Levels in U.S. Adults with or without Comorbidities, 1999–2018

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