Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis.
ABSTRACT: Environmental cadmium and lead exposures are widespread, and both metals are nephrotoxic at high exposure levels. Few studies have evaluated the associations between low-level cadmium and clinical renal outcomes, particularly with respect to joint cadmium and lead exposure. The geometric mean levels of blood cadmium and lead were 0.41 microg/L (3.65 nmol/L) and 1.58 microg/dL (0.076 micromol/L), respectively, in 14,778 adults aged >or=20 years who participated in the National Health and Nutrition Examination Survey (1999-2006). After adjustment for survey year, sociodemographic factors, chronic kidney disease risk factors, and blood lead, the odds ratios for albuminuria (>or=30 mg/g creatinine), reduced estimated glomerular filtration rate (eGFR) (<60 mL/minute/1.73 m(2)), and both albuminuria and reduced eGFR were 1.92 (95% confidence interval (CI): 1.53, 2.43), 1.32 (95% CI: 1.04, 1.68), and 2.91 (95% CI: 1.76, 4.81), respectively, comparing the highest with the lowest blood cadmium quartiles. The odds ratios comparing participants in the highest with the lowest quartiles of both cadmium and lead were 2.34 (95% CI: 1.72, 3.18) for albuminuria, 1.98 (95% CI: 1.27, 3.10) for reduced eGFR, and 4.10 (95% CI: 1.58, 10.65) for both outcomes. These findings support consideration of cadmium and lead as chronic kidney disease risk factors in the general population and provide novel evidence of risk with environmental exposure to both metals.
Project description:<h4>Background</h4>Metals have been shown to have a wide range of neurologic effects across the life course, but most studies consider neurodevelopment or neurodegenerative diseases in older adults. We investigated exposure to metals during adulthood in association with subclinical neurologic endpoints, considering the metals individually and as a mixture, and potential interactions among exposures.<h4>Methods</h4>We measured blood levels of cadmium, lead, mercury, manganese, and selenium in 1007 Gulf state residents and estimated cross-sectional associations between ranked levels of blood metals and the presence of self-reported neurologic symptoms. Single pollutant models were mutually adjusted for other metals and we used quantile g-computation to evaluate associations with exposure to the combined mixture. In stratified analyses, we assessed heterogeneity by smoking and blood selenium.<h4>Results</h4>The highest quartile of cadmium was associated with a higher prevalence of central nervous system symptoms (prevalence ratio [PR] = 1.50; 95% confidence interval [CI] = 1.13, 1.99), with stronger associations among nonsmokers (PR = 1.63; 95% CI = 1.11, 2.38) and those with low selenium (PR = 2.29, 95% CI = 1.50, 3.49). Selenium also modified associations between lead and peripheral nervous system symptoms, with increased symptoms in the low selenium group at all quartiles of exposure (<i>P</i>-trend = 0.07). Conversely, those with the highest co-exposure to mercury and selenium had reduced neurologic symptoms (PR = 0.73, 95% CI = 0.55, 0.96). Results of the mixture analysis were consistent with single chemical results.<h4>Conclusions</h4>Cadmium exhibited the most consistent relationship with increased neurologic symptoms, though lead was an important exposure in subgroup analyses. Selenium may modify subclinical neurotoxic effects of metals at non-occupational levels in adults.
Project description:<h4>Background</h4>The prevalence of hearing loss increases rapidly with aging. Hearing loss is common in all age groups, even in young adults and adolescents. A growing body of evidence has suggested that heavy metals have ototoxic effects, yet few epidemiological studies have investigated the association between heavy metals and hearing loss in a general population that includes adults and adolescents.<h4>Objectives</h4>We examined the association between environmental exposures to lead, mercury, and cadmium and the risk of hearing loss in adults and adolescents while controlling for potential confounding factors, including noise exposures and clinical factors.<h4>Methods</h4>We analyzed cross-sectional data from 5,187 adults and 853 adolescents in the Korean National Health and Nutrition Examination Survey 2010-2012. Pure-tone average (PTA) of hearing thresholds at high frequency (3, 4, and 6 kHz) were computed, and hearing loss was defined as a PTA>25?dB in adults and PTA>15?dB in adolescents.<h4>Results</h4>In adults, the highest (vs. lowest) quartiles of blood lead and cadmium were associated with 1.70 (95% CI: 1.25, 2.31) and 1.47 (95% CI: 1.05, 2.05) odds ratios for high-frequency hearing loss (p-trend<0.001?and=0.007), respectively. In adolescents, the highest quartile (vs. lowest) of blood cadmium had an odds ratio of 3.03 (95% CI: 1.44, 6.40) for high-frequency hearing loss (<i>p</i>-trend=0.003), but blood lead was not associated with hearing loss. No significant association between blood mercury and hearing loss was suggested in either adults or adolescents.<h4>Conclusions</h4>The results of the present study suggest that exposure to environmental lead and cadmium in adults and exposure to environmental cadmium in adolescents may play a role in the risk of hearing loss. https://doi.org/10.1289/EHP565.
Project description:Elevated red blood cell distribution width (RDW), traditionally an indicator of anemia, has now been recognized as a risk marker for cardiovascular disease incidence and mortality. Experimental and acute exposure studies suggest that cadmium and lead individually affect red blood cell production; however, associations between environmental exposures and RDW have not been explored. We evaluated relationships of environmental cadmium and lead exposures to RDW. We used data from 24,607 participants aged ?20 years in the National Health and Nutrition Examination Survey (2003-2016) with information on blood concentrations of cadmium and lead, RDW and socio-demographic factors. In models adjusted for age, sex, race/ethnicity, education, poverty income ratio, BMI, alcohol consumption, smoking status and serum cotinine, RDW was increasingly elevated across progressively higher quartiles of blood cadmium concentration. A doubling of cadmium concentration was associated with 0.16 higher RDW (95% CI: 0.14, 0.18) and a doubling of lead concentration with 0.04 higher RDW (95% CI: 0.01, 0.06). Also, higher cadmium and lead concentrations were associated with increased odds of high RDW (RDW>14.8%). The associations were more pronounced in women and those with low-to-normal mean corpuscular volume (MCV) and held even after controlling for iron, folate or vitamin B12 deficiencies. In analysis including both metals, cadmium remained associated with RDW, whereas the corresponding association for lead was substantially attenuated. In this general population sample, blood cadmium and lead exposures were positively associated with RDW. The associations may indicate hemolytic or erythropoietic mechanisms by which exposure increases mortality risk.
Project description:To examine the relationship between cadmium, lead, and mercury concentrations with high-sensitivity C-reactive protein (hs-CRP) and homocysteine in women.Metals were measured at enrollment in whole blood. Homocysteine and hs-CRP were measured in one (N = 9) or two (N = 250) menstrual cycles up to 3 and 8 times per cycle, respectively. Linear mixed models with inverse probability of exposure weights to account for time varying confounding were used and models were stratified by dietary and serum vitamin status (dietary: vitamin B6, B12, folate; serum: folate).Geometric mean (95% confidence interval (CI)) concentrations for cadmium, lead, and mercury were 0.29 (0.26-0.31) μg/L, 0.91 (0.86-0.96) μg/dL, and 1.05 (0.93-1.18) μg/L, respectively. Lead was associated with increased homocysteine (0.08; 95% CI: 0.01, 0.15) and this persisted among those in the lower three quartiles of consumption of vitamin B6, B12, folate, and serum folate but was not significant among those in the upper quartile. No associations were observed between metals and hs-CRP.Blood lead was associated with increased homocysteine in a cohort of healthy, premenopausal women but these associations did not persist among those consuming ≥75th percentile of essential micronutrients. Cadmium, lead, and mercury were not associated with hs-CRP concentrations.
Project description:Renal hyperfiltration, which is associated with renal injury, occurs in diabetic or obese individuals. Serum alkaline phosphatase (ALP) level is also elevated in patients with diabetes (DM) or metabolic syndrome (MS), and increased urinary excretion of ALP has been demonstrated in patients who have hyperfiltration and tubular damage. However, little was investigated about the association between hyperfiltration and serum ALP level. A retrospective observational study of the 21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008-2011) was performed. Renal hyperfiltration was defined as exceeding the age- and sex-specific 97.5th percentile. We divided participants into 4 groups according to their estimated glomerular filtration rate (eGFR): >120, 90-119, 60-89, and <60 mL/min/1.73 m2. The participants with eGFR >120 mL/min/1.73 m2 showed the highest risk for MS, in the highest ALP quartiles (3.848, 95% CI, 1.876-7.892), compared to the lowest quartile. Similarly, the highest risk for DM, in the highest ALP quartiles, was observed in participants with eGFR >120 ml/min/1.73 m2 (2.166, 95% CI, 1.084-4.329). ALP quartiles were significantly associated with albuminuria in participants with eGFR ? 60 ml/min/1.73m2. The highest ALP quartile had a 1.631-fold risk elevation for albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005). After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for renal hyperfiltration (95% CI, 1.204-2.192, P = 0.002). In addition, hyperfiltration was significantly associated with hemoglobin, triglyceride, white blood cell count, DM, smoking, and alcohol consumption (P<0.05). The relationship between serum ALP and metabolic disorders is stronger in participants with an upper-normal range of eGFR. Higher ALP levels are significantly associated with renal hyperfiltration in Korean general population.
Project description:Cadmium and lead are ubiquitous environmental contaminants that might increase risks of cardiovascular disease and other aging-related diseases, but their relationships with leukocyte telomere length (LTL), a marker of cellular aging, are poorly understood. In experimental studies, they have been shown to induce telomere shortening, but no epidemiologic study to date has examined their associations with LTL in the general population. We examined associations of blood lead and cadmium (n = 6,796) and urine cadmium (n = 2,093) levels with LTL among a nationally representative sample of US adults from the National Health and Nutrition Examination Survey (1999-2002). The study population geometric mean concentrations were 1.67 µg/dL (95% confidence interval (CI): 1.63, 1.70) for blood lead, 0.44 µg/L (95% CI: 0.42, 0.47) for blood cadmium, and 0.28 µg/L (95% CI: 0.27, 0.30) for urine cadmium. After adjustment for potential confounders, the highest (versus lowest) quartiles of blood and urine cadmium were associated with -5.54% (95% CI: -8.70, -2.37) and -4.50% (95% CI: -8.79, -0.20) shorter LTLs, respectively, with evidence of dose-response relationship (P for trend < 0.05). There was no association between blood lead concentration and LTL. These findings provide further evidence of physiological impacts of cadmium at environmental levels and might provide insight into biological pathways underlying cadmium toxicity and chronic disease risks.
Project description:BACKGROUND:Toxic metals show evidence of carcinogenic and estrogenic properties. However, little is known about the relationship between airborne metals and breast cancer. We evaluated the risk of breast cancer in relation to exposure to toxic metallic substances in air, individually and combined, in a US-wide cohort. METHODS:Sister Study participants (n = 50,884), breast cancer-free women who had a sister with breast cancer were recruited, from 2003 to 2009. The 2005 Environmental Protection Agency National Air Toxic Assessment's census-tract estimates of metal concentrations in air (antimony, arsenic, cadmium, chromium, cobalt, lead, manganese, mercury, nickel, and selenium) were matched to participants' enrollment residence. We used Cox regression to estimate the association between quintiles of individual metals and breast cancer incidence and weighted quantile sum regression to model the association between the metal mixture and breast cancer. RESULTS:A total of 2,587 breast cancer cases were diagnosed during follow-up (mean = 7.4 years). In individual chemical analyses comparing the highest to lowest quintiles, postmenopausal breast cancer risk was elevated for mercury (hazard ratio [HR] = 1.3, 95% confidence interval [CI], 1.1, 1.5), cadmium (HR = 1.1, 95% CI, 0.96, 1.3), and lead (HR = 1.1, 95% CI, 0.98, 1.3). The weighted quantile sum index was associated with postmenopausal breast cancer (odds ratio [OR] = 1.1, 95% CI, 1.0, 1.1). Consistent with the individual chemical analysis, the most highly weighted chemicals for predicting postmenopausal breast cancer risk were lead, cadmium, and mercury. Results were attenuated for overall breast cancer. CONCLUSIONS:Higher levels of some airborne metals, specifically mercury, cadmium, and lead, were associated with a higher risk of postmenopausal breast cancer.
Project description:BACKGROUND:Epidemiologic studies suggest toxic metals are linked with diabetes and cardiovascular disease, while experimental studies indicate nutritionally essential metals are involved in the metabolism of macronutrients and defense against oxidative stress. OBJECTIVES:We sought to evaluate how essential and toxic metals are cross-sectionally related to metabolic syndrome, a clustering of cardiometabolic conditions. METHODS:Using data from the 2011-2014 National Health and Nutrition Examination Survey (n?=?1088), we characterized metal concentrations as measured in spot urine (arsenic, cadmium, and inorganic/elemental mercury), whole blood (manganese, lead, methylmercury, and selenium), and serum (copper and zinc) samples. Principal component analysis was performed to derive patterns of exposures. Metabolic syndrome was defined according to the 2009 Joint Scientific Statement as the presence of ??3 of the following conditions: high blood pressure, high triglycerides, low HDL cholesterol, high fasting glucose, and abdominal obesity. RESULTS:After adjustment for potential confounders, prevalence ratios for metabolic syndrome comparing the highest to the lowest quartiles were 1.41 (95% CI: 1.18-1.67) for the arsenic-inorganic/elemental mercury pattern, 0.95 (0.78-1.16) for the methylmercury-manganese pattern, 0.73 (0.57-0.94) for the cadmium-lead pattern, 0.91 (0.76-1.10) for the copper pattern, and 1.36 (1.13-1.63) for the selenium-zinc pattern. The positive associations observed for the arsenic-inorganic/elemental mercury pattern were due to an elevated prevalence of high blood pressure, low HDL cholesterol, and high triglycerides among those with greater exposures. Associations for the selenium-zinc pattern were driven by a positive relationship with high triglycerides. Greater lead-cadmium co-exposures were related to a lower prevalence of dyslipidemia and abdominal obesity. CONCLUSIONS:These cross-sectional findings suggest both toxic and essential metal exposures may contribute to cardiometabolic health, but need to be confirmed with prospective data.
Project description:BACKGROUND:Environmental factors contributing to diabetic kidney disease are incompletely understood. We investigated whether blood cadmium and lead concentrations were associated with the prevalence of diabetic kidney disease, and to what extent lifestyle-related exposures (diet and smoking) contribute to blood cadmium and lead concentrations. MATERIAL AND METHODS:In a cross-sectional analysis in 231 patients with type 2 diabetes included in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1), blood cadmium and lead concentrations were determined using inductively coupled plasma mass spectrometry. The associations between diet (derived from food frequency questionnaire), smoking and cadmium and lead were determined using multivariate linear regression. The associations between cadmium and lead and diabetic kidney disease (albumin excretion >30 mg/24 h and/or creatinine clearance <60 mL/min/1.73 m2) were determined using multivariate logistic regression. RESULTS:Median blood concentrations were 2.94 nmol/L (interquartile range (IQR): 1.78-4.98 nmol/L) for cadmium and 0.07 µmol/L (IQR: 0.04-0.09 µmol/L) for lead, i.e., below acute toxicity values. Every doubling of lead concentration was associated with a 1.75 (95% confidence interval (CI): 1.11-2.74) times higher risk for albuminuria. In addition, both cadmium (odds ratio (OR) 1.50 95% CI: 1.02-2.21) and lead (OR 1.83 95% CI: 1.07-3.15) were associated with an increased risk for reduced creatinine clearance. Both passive smoking and active smoking were positively associated with cadmium concentration. Alcohol intake was positively associated with lead concentration. No positive associations were found between dietary intake and cadmium or lead. CONCLUSIONS:The association between cadmium and lead and the prevalence of diabetic kidney disease suggests cadmium and lead might contribute to the development of diabetic kidney disease. Exposure to cadmium and lead could be a so far underappreciated nephrotoxic mechanism of smoking and alcohol consumption.
Project description:Exposure to heavy metals from environmental and industrial sources remains a concern of serious public health risk. This study was conducted to analysis the relationship between heavy metal concentrations and bone density.This study used data from a nation-based sample of Koreans (n=2,429) from 2008 to 2011 Korea National Health and Nutrition Examination Survey. We were obtained heavy metals (lead, mercury and cadmium), socioeconomic and demographic factors and bone mineral density (BMD) measured by T-score.Menopausal women, current smoker or the frequent alcohol drinking, low educational level and low family income were greater in the osteopenia or osteoporosis groups than normal group, and were associated with an increased blood heavy metal concentration levels. The highest quartile group in blood lead had a 1.47 times (95% confidence interval [CI] 1.16-1.87) risk of osteopenia or osteoporosis. In case of blood cadmium, the risk for osteopenia or osteoporosis increased 2.1 times (95% CI 1.64-2.68).We observed a significant association between blood heavy metals (lead and cadmium) levels and low BMD. Our findings suggest that heavy metal exposure may be a risk factor for osteoporosis.