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      Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006

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          Abstract

          Background

          Environmental factors have been associated with the outbreak of chronic kidney disease (CKD). We evaluated the association of Cadmium (Cd) exposure with the risk of CKD in U.S. adults who participated in the 1999-2006 National Health and Nutrition Examination Surveys (NHANES).

          Methods

          5426 subjects ≥ 20 years were stratified for values of urinary and blood Cd and a multivariate logistic regression was performed to test the association between blood and urinary Cd, CKD and albuminuria (ALB) after adjustment for age, gender, race/ethnicity, body mass index and smoking habits.

          Results

          Subjects with urinary Cd > 1 mcg/g and subjects with blood Cd > 1 mcg/L showed a higher association with ALB (OR 1.63, 95% CI 1.23, 2.16; P = 0.001). Subjects with blood Cd > 1 mcg/L showed a higher association with both CKD (OR 1.48, 95% CI 1.01, 2.17; P = 0.046) and ALB (OR 1.41, 95% CI 1.10, 1.82; P = 0.007). An interaction effect on ALB was found for high levels of urinary and blood Cd ( P = 0.014).

          Conclusions

          Moderately high levels of urinary and blood Cd are associated with a higher proportion of CKD and ALB in the United States population.

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          Combining GFR and albuminuria to classify CKD improves prediction of ESRD.

          Stein I Hallan, Eberhard Ritz, Stian Lydersen … (2009)
          Despite the high prevalence of chronic kidney disease (CKD), relatively few individuals with CKD progress to ESRD. A better understanding of the risk factors for progression could improve the classification system of CKD and strategies for screening. We analyzed data from 65,589 adults who participated in the Nord-Trøndelag Health (HUNT 2) Study (1995 to 1997) and found 124 patients who progressed to ESRD after 10.3 yr of follow-up. In multivariable survival analysis, estimated GFR (eGFR) and albuminuria were independently and strongly associated with progression to ESRD: Hazard ratios for eGFR 45 to 59, 30 to 44, and 15 to 29 ml/min per 1.73 m(2) were 6.7, 18.8, and 65.7, respectively (P < 0.001 for all), and for micro- and macroalbuminuria were 13.0 and 47.2 (P < 0.001 for both). Hypertension, diabetes, male gender, smoking, depression, obesity, cardiovascular disease, dyslipidemia, physical activity and education did not add predictive information. Time-dependent receiver operating characteristic analyses showed that considering both the urinary albumin/creatinine ratio and eGFR substantially improved diagnostic accuracy. Referral based on current stages 3 to 4 CKD (eGFR 15 to 59 ml/min per 1.73 m(2)) would include 4.7% of the general population and identify 69.4% of all individuals progressing to ESRD. Referral based on our classification system would include 1.4% of the general population without losing predictive power (i.e., it would detect 65.6% of all individuals progressing to ESRD). In conclusion, all levels of reduced eGFR should be complemented by quantification of urinary albumin to predict optimally progression to ESRD.
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            Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate.

            Brad C. Astor, Josef Coresh, Frederick Van Lente … (2002)
            Equations using serum creatinine level, age, sex, and other patient characteristics often are used to estimate glomerular filtration rate (GFR) in both clinical practice and research studies. However, the critical dependence of these equations on serum creatinine assay calibration often is overlooked, and the reproducibility of estimated GFR is rarely discussed. We address these issues in frozen samples from 212 Modification of Diet in Renal Disease (MDRD) study participants and 342 Third National Health and Nutrition Examination Survey (NHANES III) participants assayed for serum creatinine level a second time during November 2000. Variation in serum creatinine level was assessed in 1,919 NHANES III participants who had serum creatinine measured on two visits a median of 17 days apart. Linear regression was used to compare estimates. Calibration of serum creatinine varied substantially across laboratories and time. Data indicate that serum creatinine assays on the same samples were 0.23 mg/dL higher in the NHANES III than MDRD study. Data from the College of American Pathologists suggest that a difference of this magnitude across laboratories is not unusual. Conversely, serum creatinine assays an average of 2 weeks apart have better precision (SD of percentage of difference in estimated GFR, 15%; 90% of estimates within 21%). Errors in calibration make little difference in estimating severely decreased GFR (<30 mL/min/1.73 m2), but result in progressively larger differences at higher GFRs. Both clinical and research use of serum creatinine or equations to estimate GFR require knowledge of the calibration of the serum creatinine assay. Copyright 2002 by the National Kidney Foundation, Inc.
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              Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis.

              Eliseo Guallar, Ana Navas-Acien, V Weaver … (2009)
              Environmental cadmium and lead exposures are widespread, and both metals are nephrotoxic at high exposure levels. Few studies have evaluated the associations between low-level cadmium and clinical renal outcomes, particularly with respect to joint cadmium and lead exposure. The geometric mean levels of blood cadmium and lead were 0.41 microg/L (3.65 nmol/L) and 1.58 microg/dL (0.076 micromol/L), respectively, in 14,778 adults aged >or=20 years who participated in the National Health and Nutrition Examination Survey (1999-2006). After adjustment for survey year, sociodemographic factors, chronic kidney disease risk factors, and blood lead, the odds ratios for albuminuria (>or=30 mg/g creatinine), reduced estimated glomerular filtration rate (eGFR) (<60 mL/minute/1.73 m(2)), and both albuminuria and reduced eGFR were 1.92 (95% confidence interval (CI): 1.53, 2.43), 1.32 (95% CI: 1.04, 1.68), and 2.91 (95% CI: 1.76, 4.81), respectively, comparing the highest with the lowest blood cadmium quartiles. The odds ratios comparing participants in the highest with the lowest quartiles of both cadmium and lead were 2.34 (95% CI: 1.72, 3.18) for albuminuria, 1.98 (95% CI: 1.27, 3.10) for reduced eGFR, and 4.10 (95% CI: 1.58, 10.65) for both outcomes. These findings support consideration of cadmium and lead as chronic kidney disease risk factors in the general population and provide novel evidence of risk with environmental exposure to both metals.
              Article 0 comments Cited 106 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMC Public Health
                Title: BMC Public Health
                Publisher: BioMed Central
                ISSN (Electronic): 1471-2458
                Publication date Collection: 2010
                Publication date (Electronic): 3 June 2010
                Volume: 10
                Page: 304
                Affiliations
                [1 ]Division of Nephrology and Dialysis, Columbus-Gemelli University Hospital, Renal Program, Catholic University, Rome, Italy
                Article
                Publisher ID: 1471-2458-10-304
                DOI: 10.1186/1471-2458-10-304
                PMC ID: 2887827
                PubMed ID: 20525263
                SO-VID: a22745c4-8851-4fc6-bb8e-8666e8a443ee
                Copyright © Copyright ©2010 Ferraro et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 2 December 2009
                Date accepted : 3 June 2010
                Categories
                Subject: Research article

                ScienceOpen disciplines: Public health
                Data availability:
                ScienceOpen disciplines: Public health

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