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Sökning: WFRF:(Barregård Lars) > Sällsten Gerd 1952

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  • Akerstrom, Magnus, et al. (författare)
  • Associations between Urinary Excretion of Cadmium and Proteins in a Nonsmoking Population: Renal Toxicity or Normal Physiology?
  • 2013
  • Ingår i: Environmental Health Perspectives. - National Institute of Environmental Health Science. - 1552-9924. ; 121:2, s. 187-191
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Associations between cadmium (Cd) and kidney function have been reported even at low levels of exposure in the general population. Recently, the causality of these associations has been questioned. OBJECTIVES: We examined associations between urinary Cd (U-Cd; a biomarker of exposure) and urinary proteins that are used as biomarkers of kidney effects, based on repeated short-term sampling in healthy subjects. METHODS: Twenty-four hour urine samples were collected on 2 separate days at six fixed times from 30 healthy nonsmoking men and women (median age 39 years). We analyzed the samples (N = 354) for Cd (i.e., U-Cd) and two proteins used as kidney function biomarkers: urinary albumin (U-Alb) and alpha-1-microglobulin (U-A1M). Concentrations were adjusted for creatinine concentration or for specific gravity, and excretion rates (mass per hour) were calculated. Possible associations were assessed within each individual participant, and mean correlations and regressions were evaluated. RESULTS: We found clear positive mean associations within individuals between the excretion of U-Cd [mean, 0.11 mu g/g creatinine (range, 0.01-0.52 mu g/g creatinine)] and both U-Alb and U-A1M. The associations were stronger for excretion rates and concentrations adjusted for specific gravity than for concentrations adjusted for creatinine. We also found significant positive associations of urinary flow with excretion of U-Cd, U-Alb, and U-A1M. CONCLUSIONS: Associations between short-term changes in U-Cd and markers of kidney function within individual nonsmoking study participants are unlikely to reflect effects of Cd toxicity. A more likely explanation is that these associations result from normal variation in renal function, including changes in urinary flow, that influence the urinary excretion of both Cd and proteins in the same direction. These effects of normal variability may result in overestimation of the adverse effects of Cd on kidney function at low-level Cd exposure.
  • Akerstrom, Magnus, et al. (författare)
  • Relationship between mercury in kidney, blood, and urine in environmentally exposed individuals, and implications for biomonitoring
  • 2017
  • Ingår i: Toxicology and Applied Pharmacology. - 0041-008X. ; 320, s. 17-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Individuals without occupational exposure are exposed to mercury (Hg) from diet and dental amalgam. The kidney is a critical organ, but there is limited information regarding the relationship between Hg in kidney (K-Hg), urine (U-Hg), blood (B-Hg), and plasma (P-Hg). Objectives The aim was to determine the relationship between K-Hg, U-Hg, B-Hg, and P-Hg among environmentally exposed individuals, estimate the biological half-time of K-Hg, and provide information useful for biomonitoring of Hg. Methods Kidney cortex biopsies and urine and blood samples were collected from 109 living kidney donors. Total Hg concentrations were determined and the relationships between K-Hg, U-Hg, P-Hg, and B-Hg were investigated in regression models. The half-time of K-Hg was estimated from the elimination constant. Results There were strong associations between K-Hg and all measures of U-Hg and P-Hg (rp = 0.65–0.84, p < 0.001), while the association with B-Hg was weaker (rp = 0.29, p = 0.002). Mean ratios between K-Hg (in μg/g) and U-Hg/24h (in μg) and B-Hg (in μg/L) were 0.22 and 0.19 respectively. Estimates of the biological half-time varied between 30 and 92 days, with significantly slower elimination in women. Adjusting overnight urine samples for dilution using urinary creatinine resulted in less bias in relation to K-Hg or U-Hg/24h, compared with other adjustment techniques. Conclusions The relationship between K-Hg and U-Hg is approximately linear. K-Hg can be estimated using U-Hg and gender. Women have longer half-time of Hg in kidney compared to men. Adjusting overnight urine samples for creatinine concentration resulted in less bias.
  • Akerstrom, Magnus, et al. (författare)
  • Sampling of urinary cadmium: differences between 24-h urine and overnight spot urine sampling, and impact of adjustment for dilution
  • 2012
  • Ingår i: International Archives of Occupational and Environmental Health. - Springer. - 1432-1246. ; 85:2, s. 189-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Urinary cadmium (U-Cd) sampling can be done either by 24-h urine or spot urine sampling, and adjustment for dilution is usually needed. The choice of sampling period and adjustment technique could, however, potentially induce bias. The aim of the study was to compare 24-h urine and spot urine sampling and two dilution adjustment techniques, when assessing U-Cd. Separate 24-h urine (U24) and timed overnight spot urine (UON) samples were collected from 152 healthy kidney donors. U-Cd, creatinine concentration (U-Crea) and specific gravity (SG) were analysed. Differences between U24 and UON samples were tested using paired t test, and the effect of urinary flow rate (UF) was assessed by linear regression. The cadmium excretion rate (U-Cd/h) was lower in the UON than in U24 samples (mean 0.017 mu g/h vs. 0.021 mu g/h; p < 0.001). This decrease was found also for the creatinine-adjusted U-Cd (U-CdCrea) (mean 0.36 mu g/gC and 0.41 mu g/gC; p < 0.001). For U-Cd adjusted for specific gravity (U-CdSG), the difference was reversed, but not statistically significant. The creatinine excretion rate (U-Crea/h) decreased at low UF, especially in the UON. Since U-Cd/h was lower in UON than in U24 samples, the former will underestimate the true Cd excretion. This was seen for U-CdCrea but not for U-CdSG. However, it may be an advantage that the U-CdSG is similar, irrespective of sampling strategy. At low UF, U-CdCrea will be biased upwards. Whether U24 or UON samples adjusted for U-Crea or SG best reflect kidney-Cd is still unknown.
  • Akerstrom, Magnus, et al. (författare)
  • The relationship between cadmium in kidney and cadmium in urine and blood in an environmentally exposed population
  • 2013
  • Ingår i: Toxicology and Applied Pharmacology. - Academic Press. - 1096-0333. ; 268:3, s. 286-293
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Cadmium (Cd) is toxic to the kidney and a major part of the body burden occurs here. Cd in urine (U-Cd) and blood (B-Cd) are widely-used biomarkers for assessing Cd exposure or body burden. However, empirical general population data on the relationship between Cd in kidney (K-Cd), urine, and blood are scarce. Our objectives were to determine the relationship between cadmium in kidney, urine, and blood, and calculate the elimination half-time of Cd from the kidney. Methods: Kidney cortex biopsies, urine, and blood samples were collected from 109 living kidney donors. Cd concentrations were determined and the relationships between K-Cd, U-Cd, and B-Cd were investigated in regression models. The half-time of K-Cd was estimated from the elimination constant. Results: There was a strong association between K-Cd and U-Cd adjusted for creatinine (r(p) = 0.70, p < 0.001), while the association with B-Cd was weaker (r(p) = 0.44, p < 0.001). The relationship between K-Cd and U-Cd was nonlinear, with slower elimination of Cd at high K-Cd. Estimates of the K-Cd half-time varied between 18 and 44 years. A K-Cd of 25 mu g/g corresponds to U-Cd of 0.42 mu g/g creatinine in overnight urine (U-Cd/K-Cd ratio: about 1:60). Multivariate models showed Cd in blood and urinary albumin as determinants for U-Cd excretion. Discussion: In healthy individuals with low-level Cd exposure, there was a strong correlation between Cd in kidney and urine, especially after adjustment for creatinine. Urinary Cd was also affected by Cd in blood and urinary albumin. Previous estimates of the U-Cd/K-Cd ratio may underestimate K-Cd at low U-Cd. (C) 2013 Elsevier Inc. All rights reserved.
  • Akerstrom, Magnus, et al. (författare)
  • Variability of urinary cadmium excretion in spot urine samples, first morning voids, and 24 h urine in a healthy non-smoking population: Implications for study design
  • 2014
  • Ingår i: Journal of Exposure Science & Environmental Epidemiology. - Nature Publishing Group. - 1559-064X. ; 24:2, s. 171-179
  • Tidskriftsartikel (refereegranskat)abstract
    • When selecting the least biased exposure surrogate, for example, the concentration of a biomarker in a urine sample, information on variability must be taken into consideration. We used mixed-effects models to estimate the variability and determinants of urinary cadmium (U-Cd) excretion using spot urine samples collected at six fixed times during 2 days about 1 week apart, from 24 healthy non-smokers. The urine samples were analysed for U-Cd, the concentrations were adjusted for dilution, and the excretion rates were calculated. Between-individual variability dominated the total variability for most measures of U-Cd excretion, especially for 24h urine and first morning samples. The U-Cd excretion showed a circadian rhythm during the day, and time point of sampling was a significant factor in the mixed-effects models, thus a standardised sampling time, such as first morning urine samples, needs to be applied. Gender, urinary flow rate, age, and urinary protein excretions were also significant determinants for U-Cd excretion. The choice of biomarker for U-Cd excretion was found to be more important in individually-based studies of exposure-response relationships than in studies of comparing Cd levels of groups. When planning a study, this variability of U-Cd in spot samples must be acknowledged.
  • Andersson, Eva M., et al. (författare)
  • Partial Mediation by Cadmium Exposure of the Association Between Tobacco Smoking and Atherosclerotic Plaques in the Carotid Artery
  • 2018
  • Ingår i: American Journal of Epidemiology. - 0002-9262 .- 1476-6256. ; 187:4, s. 806-816
  • Tidskriftsartikel (refereegranskat)abstract
    • Exposure to cadmium confers increased cardiovascular risk. Tobacco smoke contains cadmium, which, hypothetically, may mediate parts of the tobacco-associated risk of developing atherosclerotic plaques. Baseline data from the Swedish Malmö Diet and Cancer cohort (1991-1996) were used to test this hypothesis. Mediation analysis was used to examine associations between smoking and blood cadmium levels and the prevalence of ultrasound-assessed carotid atherosclerotic plaques. The total association with smoking status (never smokers, 2 categories of former smokers, and current smokers) was split into direct and indirect association, and the proportion mediated was estimated. The adjusted estimated plaque prevalence was approximately 27% among never smokers. We identified both a direct and an indirect pathway between smoking and carotid plaques; the indirect association, through cadmium, was observed among current smokers and former smokers who had quit smoking less than 15 years before. For current smokers, the prevalence ratio for plaque was 1.5, with 60%-65% of the association with smoking being mediated through cadmium. Recent former smokers had a prevalence ratio of 1.3, and 40%-45% was mediated through cadmium. Long-time former smokers had a prevalence ratio of 1.2, but none of the association was mediated through cadmium. In conclusion, about two-thirds of the proatherosclerotic association with smoking was mediated by cadmium.
  • Barregard, Lars, et al. (författare)
  • Blood cadmium levels and incident cardiovascular events during follow-up in a population-based cohort of swedish adults : : The malmö diet and cancer study
  • 2016
  • Ingår i: Environmental Health Perspectives. - National Institute of Environmental Health Science. - 0091-6765. ; 124:5, s. 594-600
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cadmium exposure may increase the risk of cardiovascular disease. The only published longitudinal study on cadmium and incident cardiovascular disease was performed in American Indians with relatively high cadmium exposure. oBjectives: Our aim was to examine the association between blood cadmium at baseline and incident cardiovascular events in a population-based study of Swedish men and women with cadmium levels similar to those of most European and U.S. populations. Methods: A Swedish population-based cohort (n = 6,103, age 46-67 years) was recruited between 1991 and 1994. After we excluded those with missing data on smoking, 4,819 participants remained. Acute coronary events, other major cardiac events, stroke, and cardiovascular mortality were followed until 2010. Associations with blood cadmium (estimated from cadmium in erythrocytes) were analyzed using Cox proportional hazards regression including potential confounders and important cardiovascular risk factors. results: Hazard ratios for all cardiovascular end points were consistently increased for participants in the 4th blood cadmium quartile (median, 0.99 μg/L). In models that also included sex, smoking, waist circumference, education, physical activity, alcohol intake, serum triglycerides, HbA1c, and C-reactive protein, the hazard ratios comparing the highest and lowest quartiles of exposure were 1.8 (95% CI: 1.2, 2.7) for acute coronary events, and 1.9 (1.3, 2.9) for stroke. Hazard ratios in never-smokers were consistent with these estimates. conclusions: Blood cadmium in the highest quartile was associated with incident cardiovascular disease and mortality in our population-based samples of Swedish adults. The consistent results among never-smokers are important because smoking is a strong confounder. Our findings suggest that measures to reduce cadmium exposures are warranted, even in populations without unusual sources of exposure.
  • Barregard, Lars, et al. (författare)
  • Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources.
  • 2010
  • Ingår i: Environmental research. - 1096-0953. ; 110:1, s. 47-54
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. Objectives: To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors. Methods: Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and cold vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam. fish consumption, and iron stores were evaluated. Results: The median kidney concentrations were 12.9 mu g/g (wet weight) for cadmium, 0.21 mu g/g for mercury, and 0.08 mu g/g for lead. Kidney Cd increased by 3.9 mu g/g for a 10 year increase in age, and by 3.7 mu g/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5 mu g/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed. Conclusions: In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure. (C) 2009 Elsevier Inc. All rights reserved.
  • Bergström, Göran, et al. (författare)
  • Is cadmium exposure associated with the burden, vulnerability and rupture of human atherosclerotic plaques?
  • 2015
  • Ingår i: PloS one. - 1932-6203. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The general population is exposed to cadmium from food and smoking. Cadmium is a widely spread toxic pollutant that seems to be associated with cardiovascular diseases, although little is known if it contributes to the occurrence of atherosclerotic plaques and the process whereby plaques become vulnerable and are prone to rupture. We tested the hypotheses that cadmium exposure is associated not only with an increased subclinical burden of atherosclerotic plaques in different vascular territories and early signs of plaque vulnerability, but also with cadmium content and plaque-rupture in the clinical phase of the disease. Ultrasound technique was used to measure plaque prevalence and echogenicity in the carotid and femoral arteries in a population sample of women (n = 599) in whom blood cadmium was measured. In addition cadmium was measured in snap-frozen endarterectomies and whole blood obtained from patients who were referred to surgery because of symptomatic carotid plaques (n = 37). Sixteen endarterectomies were divided into three parts corresponding to different flow conditions and plaque vulnerability. In the population sample blood cadmium was associated with the number of vascular territories with plaques (p = 0.003 after adjustment for potential confounders). The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (p<0.001). Compared with the other parts of the plaque, the cadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque where rupture often occurs.
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