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Objectives: The nephrotoxicity of cadmium at low levels of exposure, measured by urinary cadmium, has recently been questioned since co-excretion of cadmium and proteins may have causes other than cadmium toxicity. The aim of this study was to explore the relation between kidney function and low or moderate cadmium levels, measured directly in kidney biopsies., Methods: We analysed cadmium in kidney biopsies (K-Cd), blood (B-Cd) and urine (U-Cd) from 109 living kidney donors in a cross-sectional study. We measured glomerular filtration rate (GFR), cystatin C in serum, albumin, β-2-microglobulin (B2M), retinol-binding protein (RBP), α-1-microglobulin (A1M), N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 (KIM-1) in 24 h and overnight urine., Results: We found significant positive associations between A1M excretion and K-Cd in multiple regression models including age, sex, weight, smoking and urinary flow rate. This association was also present in never-smokers. A1M was also positively associated with B-Cd and U-Cd. GFR and the other biomarkers of kidney function were not associated with K-Cd. GFR estimated from serum cystatin C showed a very poor correlation with measured GFR. KIM-1, RBP and possibly albumin were positively associated with U-Cd, but only in overnight urine. No associations were found with B2M., Conclusions: Our results suggest that A1M in urine is a sensitive biomarker for effects of low-level cadmium exposure. A few associations between other renal biomarkers and U-Cd, but not K-Cd, were probably caused by physiological co-excretion or chance., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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 (rp=0.70, p<0.001), while the association with B-Cd was weaker (rp=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 44years. A K-Cd of 25μg/g corresponds to U-Cd of 0.42μg/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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Cadmium (Cd) can cause renal damage and osteoporosis after high-level exposure. Recently such effects, including increased urinary excretion of calcium, have been shown also at low-level exposure, as measured by Cd in blood or urine. However, associations with kidney Cd have not been examined. The aim of this study was to explore the relation between kidney Cd and urinary calcium excretion, or bone mineral density., Methods: Cd was determined in kidney cortex biopsies from 109 living kidney donors. Serum was analyzed for ionized calcium, parathyroid hormone and vitamin D. Calcium was analyzed in overnight and 24-hour urine samples. Bone mineral density was measured in a subgroup of 67 donors. Associations between single variables were assessed by Spearman and Pearson correlation coefficients. Differences between independent groups were compared using Student's t-test. For related samples, paired t-test was applied. Associations between urinary calcium and kidney Cd, ionized serum calcium, serum parathyroid hormone, inactive and active vitamin D and background variables were assessed using multiple linear regression and logistic regression., Results: In spite of relatively low kidney Cd levels (median 13 μg/g, range 1.5-55 μg/g) kidney Cd and urinary calcium were positively associated, mainly caused by an association in women. Donors with kidney Cd above the median (subgroup mean 23 μg/g) had significantly higher excretion of urinary calcium normalized for creatinine than those below the median (subgroup mean 7.3 μg/g). In women, also the excretion of Ca per hour was higher in those with high kidney Cd (24 hour sample mean 0.21 vs. 0.15 mmol/h; overnight sample 0.16 vs. 0.11 mmol/h). There were negative associations between kidney Cd and bone mineral density, most of which, however, disappeared in multivariate analyses., Conclusions: This study provides support for an association between kidney Cd levels and urinary calcium excretion in women, but not in men. The results strengthen the case for preventive measures against Cd pollution.

Cadmium is a widespread environmental pollutant, which is associated with increased risk of osteoporosis. It has been proposed that cadmium's toxic effect on bone is exerted via impaired activation of vitamin D, secondary to the kidney effects. To test this, we assessed the association of cadmium-induced bone and kidney effects with serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D); measured by enzyme immunoassay. For the assessment, we selected 85 postmenopausal women, based on low (0.14-0.39 microg/L) or high (0.66-2.1 microg/L) urinary cadmium, within a cross-sectional population-based women's health survey in Southern Sweden. We also measured 25-hydroxy vitamin D, cadmium in blood, bone mineral density and several markers of bone remodeling and kidney effects. Although there were clear differences in both kidney and bone effect markers between women with low and high cadmium exposure, the 1,25(OH)(2)D concentrations were not significantly different (median, 111 pmol/L (5-95th percentile, 67-170 pmol/L) in low- and 125 pmol/L (66-200 pmol/L) in high-cadmium groups; p=0.08). Also, there was no association between 1,25(OH)(2)D and markers of bone or kidney effects. It is concluded that the low levels of cadmium exposure present in the studied women, although high enough to be associated with lower bone mineral density and increased bone resorption, were not associated with lower serum concentrations of 1,25(OH)(2)D. Hence, decreased circulating levels of 1,25(OH)(2)D are unlikely to be the proposed link between cadmium-induced effects on kidney and bone.

The relationships between cadmium (Cd) levels in soil, feed crops, feed concentrate, pig feed mixture, water, pig blood, and kidney from 49 farms were investigated and the possibility to use pig kidney as a bioindicator of available Cd in the agricultural environment was evaluated. There were correlations between Cd levels in soil and wheat, between wheat and barley, and between feed and kidney. The accumulation ratio between Cd levels in feed and kidney was on average 3. Animals from the same farm, raised in the same environment, given the same feed, and slaughtered at the same age had Cd levels in kidney and blood that could differ several times. This great variation, together with a considerable Cd contribution from nonlocally produced feed ingredients (concentrates), limits the possibilities to use Cd in pig kidney as an indicator of the available Cd in the local environment.

We studied determinants of cadmium status and kidney function in nonsmoking men and women living on farms in southern Sweden. Median blood Cd (BCd) was 1.8 nmol/L (range, 0.38-18) and median urinary Cd (UCd) was 0.23 nmol/mmol creatinine (range, 0.065-0.99). The intake of Cd per kilogram body weight did not significantly differ between sexes and did not correlate with BCd or UCd, which may be explained by a low and varying bioavailibility of Cd from food items. However, when a subgroup of the study population, couples of never-smoking men and women, were compared, a lower intake per kilogram body weight was found in the women, but the women had a 1.8 times higher BCd and a 1.4 times higher UCd. The higher female BCd and UCd may be explained by higher absorption due to low iron status. BCd and UCd both increased with age and were higher in the ex-smokers, who had stopped smoking more than 5 years before the study, compared to never-smokers. The contribution of locally produced food to the total Cd intake was relatively low and varied. Males living in areas with low soil Cd had lower UCd than the others. However, Cd levels in kidneys from pigs, fed locally produced cereals, did not predict BCd or UCd in humans at the same farms. The kidney function parameter ss2-microglobulin-creatinine clearance was related to UCd, whereas urinary protein-HC, N-acetyl-ss-glucoseaminidase or albumin-creatinine clearance was not when age was accounted for. Hence, even at the low exposure levels in this study population, there was an indication of effect on biochemical markers of renal function.

Background: Cadmium (Cd) can cause renal damage and osteoporosis after high-level exposure. Recently such effects, including increased urinary excretion of calcium, have been shown also at low-level exposure, as measured by Cd in blood or urine. However, associations with kidney Cd have not been examined. The aim of this study was to explore the relation between kidney Cd and urinary calcium excretion, or bone mineral density. Methods: Cd was determined in kidney cortex biopsies from 109 living kidney donors. Serum was analyzed for ionized calcium, parathyroid hormone and vitamin D. Calcium was analyzed in overnight and 24-hour urine samples. Bone mineral density was measured in a subgroup of 67 donors. Associations between single variables were assessed by Spearman and Pearson correlation coefficients. Differences between independent groups were compared using Student's t-test. For related samples, paired t-test was applied. Associations between urinary calcium and kidney Cd, ionized serum calcium, serum parathyroid hormone, inactive and active vitamin D and background variables were assessed using multiple linear regression and logistic regression. Results: In spite of relatively low kidney Cd levels (median 13 μg/g, range 1.5-55 μg/g) kidney Cd and urinary calcium were positively associated, mainly caused by an association in women. Donors with kidney Cd above the median (subgroup mean 23 μg/g) had significantly higher excretion of urinary calcium normalized for creatinine than those below the median (subgroup mean 7.3 μg/g). In women, also the excretion of Ca per hour was higher in those with high kidney Cd (24 hour sample mean 0.21 vs. 0.15 mmol/h; overnight sample 0.16 vs. 0.11 mmol/h). There were negative associations between kidney Cd and bone mineral density, most of which, however, disappeared in multivariate analyses. Conclusions: This study provides support for an association between kidney Cd levels and urinary calcium excretion in women, but not in men. The results strengthen the case for preventive measures against Cd pollution. [ABSTRACT FROM AUTHOR]

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 (r p = 0.65–0.84, p < 0.001), while the association with B-Hg was weaker (r p = 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. [ABSTRACT FROM AUTHOR]

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 12.9μg/g (wet weight) for cadmium, 0.21μg/g for mercury, and 0.08μg/g for lead. Kidney Cd increased by 3.9μg/g for a 10 year increase in age, and by 3.7μg/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 4.5μg/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. [Copyright &y& Elsevier]