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      Tubular and Glomerular Kidney Effects in Swedish Women with Low Environmental Cadmium Exposure

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          Abstract

          Cadmium is a well-known nephrotoxic agent in food and tobacco, but the exposure level that is critical for kidney effects in the general population is not defined. Within a population-based women’s health survey in southern Sweden (Women’s Health in the Lund Area, WHILA), we investigated cadmium exposure in relation to tubular and glomerular function, from 1999 through early 2000 in 820 women (71% participation rate) 53–64 years of age. Multiple linear regression showed cadmium in blood (median, 0.38 μg/L) and urine (0.52 μg/L; density adjusted = 0.67 μg/g creatinine) to be significantly associated with effects on renal tubules (as indicated by increased levels of human complex-forming protein and N-acetyl-β- d-glucosaminidase in urine), after adjusting for age, body mass index, blood lead, diabetes, hypertension, and regular use of nephrotoxic drugs. The associations remained significant even at the low exposure in women who had never smoked. We also found associations with markers of glomerular effects: glomerular filtration rate and creatinine clearance. Significant effects were seen already at a mean urinary cadmium level of 0.6 μg/L (0.8 μg/g creatinine). Cadmium potentiated diabetes-induced effects on kidney. In conclusion, tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk.

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          Most cited references34

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          Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.

          Serum cystatin C (Cys C) has been proposed as a simple, accurate, and rapid endogenous marker of glomerular filtration rate (GFR) in research and clinical practice. However, there are conflicting reports regarding the superiority of Cys C over serum creatinine (Cr), with a few studies suggesting no significant difference. We performed a meta-analysis of available data from various studies to compare the accuracy of Cys C and Cr in relation to a reference standard of GFR. A bibliographic search showed 46 articles until December 31, 2001. We also retrieved data from eight other studies presented and published in abstract form. The overall correlation coefficient for the reciprocal of serum Cys C (r = 0.816; 95% confidence interval [CI], 0.804 to 0.826) was superior to that of the reciprocal of serum Cr (r = 0.742; 95% CI, 0.726 to 0.758; P < 0.001). Similarly, receiver operating characteristic (ROC)-plot area under the curve (AUC) values for 1/Cys C had greater identity with the reference test for GFR (mean ROC-plot AUC for Cys C, 0.926; 95% CI, 0.892 to 0.960) than ROC-plot AUC values for 1/Cr (mean ROC-plot AUC for serum Cr, 0.837; 95% CI, 0.796 to 0.878; P < 0.001). Immunonephelometric methods of Cys C assay produced significantly greater correlations than other assay methods (r = 0.846 versus r = 0.784; P < 0.001). In this meta-analysis using currently available data, serum Cys C is clearly superior to serum Cr as a marker of GFR measured by correlation or mean ROC-plot AUC. Copyright 2002 by the National Kidney Foundation, Inc.
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            Low level exposure to cadmium and early kidney damage: the OSCAR study.

            To study the dose-response relation between cadmium dose and renal tubular damage in a population of workers and people environmentally or occupationally exposed to low concentrations of cadmium. Early kidney damage in 1021 people, occupationally or environmentally exposed to cadmium, was assessed from cadmium in urine to estimate dose, and protein HC (alpha(1)-microglobulin) in urine to assess tubular proteinuria. There was an age and sex adjusted correlation between cadmium in urine and urinary protein HC. The prevalence of tubular proteinuria ranged from 5% among unexposed people to 50% in the most exposed group. The corresponding prevalence odds ratio was 6.0 (95% confidence interval (95% CI) 1.6 to 22) for the highest exposure group, adjusted for age and sex. Multiple logistic regression analysis showed an increasing prevalence of tubular proteinuria with urinary cadmium as well as with age. After adjustment to the mean age of the study population (53 years), the results show an increased prevalence of 10% tubular proteinuria (taking into account a background prevalence of 5%) at a urinary cadmium concentration of 1.0 nmol/mmol creatinine. Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated.
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              Cadmium in blood and urine--impact of sex, age, dietary intake, iron status, and former smoking--association of renal effects.

              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.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                November 2005
                11 July 2005
                : 113
                : 11
                : 1627-1631
                Affiliations
                [1 ]Institute of Environmental Medicine, Division of Metals and Health, Karolinska Institutet, Stockholm, Sweden
                [2 ]Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden
                [3 ]Department of Clinical Chemistry, Karolinska University Hospital, Huddinge, Sweden
                [4 ]Department of Community Health, Malmö University Hospital, Malmö, Sweden
                [5 ]Department of Medicine, and
                [6 ]Department of Gynecology and Obstetrics, University Hospital, Lund, Sweden
                Author notes
                Address correspondence to A. Åkesson, Institute of Environmental Medicine, Division of Metals and Health, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden. Telephone: 46-8-524-875-42. Fax: 46-8-33-70-39. E-mail: Agneta.Akesson@imm.ki.se

                The authors declare they have no competing financial interests.

                Article
                ehp0113-001627
                10.1289/ehp.8033
                1310929
                16263522
                8c6877a6-049a-4880-9c5a-322aca26a2ff
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 21 February 2005
                : 11 July 2005
                Categories
                Research
                Environmental Medicine

                Public health
                kidney,population-based,cadmium,lead,diabetes,women,glomerular effects,environmental exposure,tubular effects,hypertension

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