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- Bergdahl, Ingvar A
(författare)
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Lead in blood. ICP-MS studies of lead in plasma, blood and erythrocyte proteins
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An inductively coupled plasma mass spectrometry (ICP-MS) method for the determination of lead in blood plasma has been developed. The detection limit was below 0.1 microgram/liter, and the precision 5%. There was no significant difference between levels in plasma and serum. Studies of individuals with varying lead exposure showed that in the general population the plasma concentrations were less than 1% of the levels in blood, and up to a few percent in highly lead-exposed individuals. There was a non-linear relationship between blood- and plasma-lead concentrations. The non-linearity could be described by a model based on high-affinity erythrocyte lead-binding proteins with a limited binding capacity. The association was relatively close, with an inter-individual variation in plasma lead of 30% relative standard deviation at a given blood-lead concentration. Neither age, sex, current lead exposure, nor the polymorphism in the delta-aminolevulinic acid dehydratase (ALAD) gene affected the distribution of lead between cells and plasma. Moreover, lead-binding erythrocyte proteins were studied by gel-chromatography with ICP-MS detection. The studies showed that the protein with the highest affinity for lead was ALAD. Together with a smaller protein, with an apparent molecular mass of 45 kDa, it bound more than half of the lead in the erythrocytes. There was also a small lead-binding component; the quantity of lead bound to it its not known. Lead in erythrocytes appeared not to be bound to hemoglobin.
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| 2. |
- Nilsson Sommar, Johan, 1983-
(författare)
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Prospective and longitudinal human studies of lead and cadmium exposure and the kidney
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cadmium and lead accumulate in humans and can have toxic effects. Exposure to cadmium is well known to cause kidney damage. Cadmium binds to metallothioneins, proteins that play a role in cadmium transport. Lead exposure’s main effect is on the central nervous system, but associations with kidney disease have also been found, although it is unknown if the latter is a causal association. The main source of both metals within the non-smoking population is from the diet.This thesis aims to 1) compare the biomarkers lead and cadmium concentration in whole-blood, plasma and urine with regard to their ability to discriminate between individuals with different mean concentrations, and to describe the effect of urinary dilution, 2) estimate the association between end-stage renal disease and blood concentrations of cadmium, lead and mercury, using prospectively collected samples for exposure evaluation, 3) use longitudinal data on kidney function makers to evaluate kidney recovery after a substantial decrease in cadmium exposure, and 4) assess the influence of metallothionein polymorphisms (MT1A rs11076161, MT2A rs10636 and MT2A rs28366003) on cadmium-associated kidney toxicity and recovery due to a reduction in Cd exposure.Repeated sampling of whole-blood, plasma and urine was conducted on 48 occupationally lead-exposed men and 20 individuals under normal environmental lead exposure, for estimation of the day-to-day and between individual-variation. Prospective samples were obtained for 118 cases that later in life developed end-stage renal disease, and 378 matched controls. Erythrocyte cadmium, lead, and mercury concentrations were determined and the risk of developing end-stage renal disease associated with metal concentrations was estimated. For evaluation of kidney recovery after a reduction in cadmium exposure and to test for gene-environment interactions, follow-up data on N-acetyl-β‑d-glucosaminidase, β2‑microglobulin, albumin, and gene polymorphisms were obtained for 412 individuals within the Chinese population and the relation to blood and urinary cadmium was assessed.The concentration of lead in blood was found to be the biomarker with the largest fraction of the total variance attributable to between-individual variation, and was therefore the biomarker with the best ability to discriminate between individuals with different mean concentrations, both for individuals under occupational and normal environmental exposure (91 and 95%, respectively). Adjusting for urinary dilution had a great effect on the fraction of the total variance attributable to between-individual variation among individuals with normal lead exposure but only a minor effect among those who were occupationally exposed. Variance analysis showed that blood concentrations were also the best discriminating biomarker for cadmium.Erythrocyte lead was, in a univariate model, associated with an increased risk of developing end-stage renal disease [odds ratio (OR) = 1.54 for an interquartile range increase, with a 95% confidence interval (CI) = 1.18-2.00], while erythrocyte mercury was negatively associated (OR = 0.75 for an interquartile range increase, with a 95% CI = 0.56-0.99). For erythrocyte cadmium, the OR was 1.15 with a 95% CI of 0.99-1.34. Associations with lead and cadmium were only seen among men. In the study on kidney recovery, the proportion of individuals with albumin level above the 95th percentile decreased between baseline and follow up, but no decrease was found for the tubular markers N-acetyl-β‑d-glucosaminidase and β2-microglobulin. Metallothionein polymorphisms modified cadmium-associated effects on N-acetyl-β‑d-glucosaminidase and β2-microglobulin levels but did not modify cadmium-associated change in any of the kidney function markers between baseline and follow up after a substantial decrease in exposure.Blood concentrations of lead and cadmium are the biomarkers with the best ability to discriminate between individuals with different mean concentrations. Adjustment for urinary dilution has great influence on the fraction of the total variance attributed to between individual variation among urine samples with low lead concentrations, but only a small influence on samples with high lead concentrations. This suggests a difference in excretion. The association between end-stage renal disease and low-level lead exposure, as assessed through prospective erythrocyte samples, gives reason for concern, although further studies are needed to determine causality. A cadmium-associated increase in albumin is reversible after a substantial reduction in exposure, but this is not the case for the observed tubular effects. The tubular kidney effects of cadmium might be modified by the MT1A rs11076161 polymorphism.
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