Laura D.K. Thomas

Early Kidney Damage in a Population Exposed to Cadmium and Other Heavy Metals

Background Exposure to heavy metals may cause kidney damage. The population living near the Avonmouth zinc smelter has been exposed to cadmium and other heavy metals for many decades. Objectives We aimed to assess Cd body burden and early signs of kidney damage in the Avonmouth population. Methods We used dispersion modeling to assess exposure to Cd. We analyzed urine samples from the local population (n = 180) for Cd (U-Cd) to assess dose (body burden) and for three biomarkers of early kidney damage [N-acetyl-β-d-glucosaminidase (U-NAG), retinol-binding protein, and α-1-microglobulin]. We collected information on occupation, intake of homegrown vegetables, smoking, and medical history by questionnaire. Results Median U-Cd concentrations were 0.22 nmol/mmol creatinine (nonsmoking 0.18/smoking 0.40) and 0.34 nmol/mmol creatinine (nonsmoking 0.31/smoking 0.46) in non-occupationally exposed men and women, respectively. There was a significant dose–response relationship between U-Cd and the prevalence of early renal damage—defined as U-NAG > 0.22 IU/mmol—with odds ratios of 2.64 [95% confidence interval (95% CI), 0.70–9.97] and 3.64 (95% CI, 0.98–13.5) for U-Cd levels of 0.3 to < 0.5 and levels ≥ 0.5 nmol/mmol creatinine, respectively (p for trend = 0.045). Conclusion U-Cd concentrations were close to levels where kidney and bone effects have been found in other populations. The dose–response relationship between U-Cd levels and prevalence of U-NAG above the reference value support the need for measures to reduce environmental Cd exposure.

Bone mineral density changes in relation to environmental PCB exposure

Background Bone toxicity has been linked to organochlorine exposure following a few notable poisoning incidents, but epidemiologic studies in populations with environmental organochlorine exposure have yielded inconsistent results. Objectives The aim of this study was to investigate whether organochlorine exposure was associated with bone mineral density (BMD) in a population 60–81 years of age (154 males, 167 females) living near the Baltic coast, close to a river contaminated by polychlorinated biphenyls (PCBs). Methods We measured forearm BMD in participants using dual energy X-ray absorptiometry; and we assessed low BMD using age- and sex-standardized Z-scores. We analyzed blood samples for five dioxin-like PCBs, the three most abundant non-dioxin-like PCBs, and p,p′-dichloro-phenyldichloroethylene (p,p′-DDE). Results In males, dioxin-like chlorobiphenyl (CB)-118 was negatively associated with BMD; the odds ratio for low BMD (Z-score less than −1) was 1.06 (95% confidence interval, 1.01–1.12) per 10 pg/mL CB-118. The sum of the three most abundant non-dioxin-like PCBs was positively associated with BMD, but not with a decreased risk of low BMD. In females, CB-118 was positively associated with BMD, but this congener did not influence the risk of low BMD in women. Conclusions Environmental organochlorine exposures experienced by this population sample since the 1930s in Sweden may have been sufficient to result in sex-specific changes in BMD.

Dietary Cadmium Exposure and Fracture Incidence Among Men : A Population-Based Prospective Cohort Study

Cadmium is an osteotoxic metal present in food. It causes multiple fractures in those highly exposed and is associated with reduced bone mineral density at considerably lower exposures. Little is known about fracture rates following low‐level cadmium exposure. We assessed the associations between dietary cadmium exposure and fracture incidence.

Dietary cadmium exposure and chronic kidney disease: A population-based prospective cohort study of men and women

The kidney is widely regarded as the critical organ for cadmium toxicity, however, considerable uncertainty remains regarding the clinical significance of the renal effects of cadmium at low levels of exposure. Food is the primary source of cadmium exposure in the general population with tobacco representing an important additional source. We aimed to assess the association between dietary cadmium exposure and chronic kidney disease (CKD) incidence in two large population-based, prospective cohorts of men (Cohort of Swedish Men (COSM)) and women (The Swedish Mammography Cohort (SMC)) with no history of kidney disease. At baseline 1997, men (45-79 years) and women (48-83 years), completed a self-administered questionnaire on diet and lifestyle. Dietary cadmium exposure for each individual was estimated using dietary data and concentrations of cadmium in food. During 13 years of follow-up, we ascertained 599 incident cases of CKD among men (in 481,591 person-years) and 253 cases among women (in 415,432 person-years) through linkage of the cohorts to national inpatient and outpatient registers. Hazard ratios (HR) were calculated using the Cox proportional-hazard regression model. Estimated dietary cadmium exposure was not associated with increased CKD incidence among men HR 0.97 (95% confidence interval (CI): 0.77-1.21) or women HR 0.74 (95% CI: 0.53-1.04), comparing highest tertile with lowest. Our results do not support a strong association between dietary cadmium exposure and CKD at the exposure levels seen in the general population.

Exposure to cadmium from food and risk of cardiovascular disease in men: a population-based prospective cohort study

Cadmium is a widely dispersed toxic metal that accumulates in the human body owing to its long biological halflife (10–30 years). Levels in food are elevated as result of farmland having become contaminated both by atmospheric deposition and the use of cadmium-containing fertilizers and sewage sludge [1]. Recently, this metal has emerged as a potential risk factor for cardiovascular disease (CVD). The diet is the main source of cadmium exposure [1]. Influenced both by the concentrations in food and by consumption patterns, dietary cadmium exposure can vary greatly between and within populations. Exposure to cadmium in the diet takes place over a lifetime and therefore even in areas with no particular cadmium contamination and where levels in food are generally low, exposure levels may be sufficient to be of public health concern. In western societies, foods such as cereals, potatoes and vegetables account for the bulk of dietary cadmium exposure owing to the frequency of their consumption. At the same time, some of these foods— especially wholegrain and vegetables—have been proposed to protect against heart-related diseases. Average dietary cadmium exposure in Sweden is similar to that observed in other parts of Europe and the US (8–25 lg/day), where no particular cadmium contamination has been reported. In Asia (Japan and China), exposure levels are commonly much higher due to the high intake of rice grown on soil contaminated by industrial processes [1]. Tobacco smoking, one of the most important CVD risk factors, also contributes to cadmium exposure due to the elevated levels in tobacco leaves and high rate of absorption from the lungs. Cadmium accumulates in endothelium and vascular smooth muscle cells, causes endothelial dysfunction in vitro and can promote atherosclerosis in vitro, in vivo and in human studies [2]. Only one previous study has assessed total cadmium exposure (measured in urine) and incident CVD, this study observed modest positive associations [3]. Two prospective studies on CVD mortality indicate some positive associations with biomarkers (blood and/or urine) of total cadmium exposure [4, 5], but overall, results are inconsistent particularly with respect to differences between the sexes. There is, therefore, a need for further studies that explore the relationship between cadmium exposure and incident CVD events in men and women separately. In addition, the risks associated with cadmium from the diet alone, remain to be assessed. We prospectively examined whether low-level dietary cadmium exposure was associated with incidence of total and specific CVD (myocardial infarction; MI and stroke) in a population-based prospective cohort of men and assessed whether tobacco smoking modified the associations. The cohort of Swedish men (COSM) has been described elsewhere [6]. In brief, 48,850 men aged 45–79 years at baseline were recruited in 1997 (response rate 49 %). Dietary intake and lifestyle data (such as education level, smoking status, height, weight, physical activity and alcohol consumption) was assessed at baseline using a selfadministered questionnaire. The validity of the food frequency questionnaire (FFQ) has been assessed in a random population-based sample of 248 men who were aged between 40 and 74 years and who lived in the study area. Each man completed the FFQ and 14 repeated 24-h recalls during a 1-year period. For macronutrients, the mean Spearman’s rank correlation coefficient was 0.65 [7]. The B. Julin (&) A. Wolk L. D. Thomas A. Åkesson Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden e-mail: bettina.julin@ki.se

Dietary cadmium exposure and kidney stone incidence: a population-based prospective cohort study of men & women.

Cadmium exposure is associated with increased urinary calcium excretion. Hypercalciuria is recognised as a major risk factor for kidney stone formation. Increased prevalence of kidney stones among those occupationally exposed to cadmium has previously been suggested. Food is the main source of cadmium exposure in the general population with tobacco representing an important additional source among smokers. We aimed to assess the association between dietary cadmium exposure and kidney stone incidence in two large population-based, prospective cohorts of men (Cohort of Swedish Men; COSM) and women (The Swedish Mammography Cohort; SMC). Those with a history of kidney stones were excluded. At baseline 1997, men (45-79yrs) and women (48 to 83yrs), completed a self-administered questionnaire on diet and lifestyle. During 12years of follow-up, we ascertained 707 cases of kidney stones in men and 290 in women through linkage of the cohorts to the national inpatient and outpatient registers. Individual dietary cadmium exposure was estimated using dietary data and concentrations of cadmium in food. Hazard ratios (HR) were calculated using the Cox proportional hazards regression models with adjustment for other risk factors. Estimated dietary cadmium exposure was not associated with increased kidney stone incidence among men HR 0.97 (95% confidence interval (CI): 0.77-1.23) or women HR 0.99 (95% CI: 0.89-1.43), comparing the highest tertile with the lowest. In conclusion, our results do not support a strong association between dietary cadmium and kidney stone risk at the exposure levels seen in the general population.

Outdoor and indoor cadmium distributions near an abandoned smelting works and their relations to human exposure.

The relationship of measured or modelled Cd concentrations in soil, house dust and available to plants with human urinary Cd concentrations were assessed in a population living around a Cd/Pb/Zn smelter in the UK. Modelled air concentrations explained 35% of soil Cd variation indicating the smelter contributed to soil Cd loads. Multi-variate analysis confirmed a significant role of biological and life-style factors in determining urinary Cd levels. Significant correlations of urinary Cd with soil, house dust and modelled plant available Cd concentrations were not, however, found. Potential reasons for the absence of clear relationships include limited environmental contact in urban populations; the role of undefined factors in determining exposure; and the limited spatial scope of the survey which did not sample from the full pollution gradient. Further, the absence of any significant relationship indicates that environmental measures provide limited advantage over atmospheric model outputs for first stage human exposure assessment.

Ascorbic acid supplements and kidney stone risk--reply.

Ascorbic Acid Supplements and Kidney Stone Risk To the Editor In their Research Letter, Thomas et al1 report an increased risk of first-episode renal stone in Swedish men who took ascorbic acid supplements (but no other supplements). This risk is almost certainly overestimated. Cases were identified according to code N20 of the International Statistical Classification of Diseases: calculus of kidney or ureter in the absence of hydroureter (www.cdc.gov/nchs/data/dvs/2006-Vol-I .pdf). Contrary to what the authors claim, the symptoms of renal colic are often nonspecific, especially in the absence of hydroureter2,3, and for this reason, nonspecific abdominal or flank pain frequently prompts an investigation for renal stone.2,3 As many as 40% of renal stones identified by means of imaging studies are asymptomatic4—not surprisingly, since the prevalence of renal stone in asymptomatic men is 10%.5 The fact that physicians and the general public are repeatedly warned that ascorbic acid supplements cause renal stones (even though the evidence is inconclusive) predictably lowers the threshold for testing for them. Thus, all other things being equal, takers of high-dose ascorbic acid supplements are much more likely than nontakers to be investigated for renal stone, artificially increasing the number of code N20 cases linked to vitamin C. These factors, combined with the authors’ sole reliance on registry entries for case identification, strongly expose their study to the important epidemiological error of “confounding by indication.”