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Rebecca Shelley,
Nam-Soo Kim,
Patrick J Parsons,
Byung-Kook Lee,
Jacqueline Agnew,
Bernard G Jaar,
Amy J Steuerwald,
Genevieve Matanoski,
Jeffrey Fadrowski,
Brian S Schwartz,
Andrew C Todd,
David Simon, Virginia M Weaver
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ABSTRACT: Uranium is a ubiquitous metal that is nephrotoxic at high doses. Few epidemiologic studies have examined the kidney filtration impact of chronic environmental exposure. In 684 lead workers environmentally exposed to uranium, multiple linear regression was used to examine associations of uranium measured in a 4-h urine collection with measured creatinine clearance, serum creatinine- and cystatin-C-based estimated glomerular filtration rates, and N-acetyl-β-D-glucosaminidase (NAG). Three methods were utilized, in separate models, to adjust uranium levels for urine concentration-μg uranium/g creatinine; μg uranium/l and urine creatinine as separate covariates; and μg uranium/4 h. Median urine uranium levels were 0.07 μg/g creatinine and 0.02 μg/4 h and were highly correlated (rs=0.95). After adjustment, higher ln-urine uranium was associated with lower measured creatinine clearance and higher NAG in models that used urine creatinine to adjust for urine concentration but not in models that used total uranium excreted (μg/4 h). These results suggest that, in some instances, associations between urine toxicants and kidney outcomes may be statistical, due to the use of urine creatinine in both exposure and outcome metrics, rather than nephrotoxic. These findings support consideration of non-creatinine-based methods of adjustment for urine concentration in nephrotoxicant research.Journal of Exposure Science and Environmental Epidemiology advance online publication, 17 April 2013; doi:10.1038/jes.2013.18.
Journal of Exposure Science and Environmental Epidemiology 04/2013; · 2.93 Impact Factor
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ABSTRACT: BACKGROUND AND OBJECTIVE:Active smoking and secondhand smoke (SHS) are known risk factors for kidney disease in adults. We evaluated the association between exposure to active smoking or SHS and kidney function in US adolescents.METHODS:This is a cross-sectional study in 7516 adolescents aged 12-17 who participated in NHANES 1999-2010 and had serum creatinine and cotinine measures. Active smoking was defined as self-reported smoking or serum cotinine concentrations >10 ng/mL. SHS was defined as nonactive smokers who self-reported living with ≥1 smokers or serum cotinine concentrations ≥ 0.05 ng/mL. Kidney function was determined by using the chronic kidney disease in children estimated glomerular filtration rate (eGFR) equation.RESULTS:Median (interquartile range) eGFR and serum cotinine concentrations were 96.8 (85.4-109.0) mL/minute per 1.73 m(2) and 0.07 (0.03-0.59) ng/mL, respectively. After multivariable adjustment, eGFR decreased 1.1 mL/minute per 1.73 m(2) (95% confidence interval [CI]: -1.8 to -0.3) per interquartile range increase in serum cotinine concentrations. The mean (95%CI) difference in eGFR for serum cotinine tertiles 1, 2, and 3 among children exposed to SHS compared to unexposed were -0.4 (-1.9 to 1.2), -0.9 (-2.7 to 0.9), and -2.2 (-4.0 to -0.4) mL/minute per 1.73 m(2), respectively (P = .03). The corresponding values among tertiles of active smokers compared to unexposed were 0.2 (-2.2 to 2.6), -1.9 (-3.8 to 0.0), and -2.6 (-4.6 to -0.6) mL/minute per 1.73 m(2) (P = .01).CONCLUSIONS:Tobacco smoke exposure was associated with decreased eGFR in US adolescents, supporting the possibility that tobacco smoke effects on kidney function begin in childhood.
PEDIATRICS 04/2013; · 4.47 Impact Factor
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Laura Y Zheng,
Jason G Umans,
Maria Tellez-Plaza,
Fawn Yeh,
Kevin A Francesconi,
Walter Goessler,
Ellen K Silbergeld,
Eliseo Guallar,
Barbara V Howard, Virginia M Weaver,
Ana Navas-Acien
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ABSTRACT: BACKGROUND: Long-term arsenic exposure is a major global health problem. However, few epidemiologic studies have evaluated the association of arsenic with kidney measures. Our objective was to evaluate the cross-sectional association between inorganic arsenic exposure and albuminuria in American Indian adults from rural areas of Arizona, Oklahoma, and North and South Dakota. STUDY DESIGN: Cross-sectional. SETTING & PARTIPANTS: Strong Heart Study locations in Arizona, Oklahoma, and North and South Dakota. 3,821 American Indian men and women aged 45-74 years with urine arsenic and albumin measurements. PREDICTOR: Urine arsenic. OUTCOMES: Urine albumin-creatinine ratio and albuminuria status. MEASUREMENTS: Arsenic exposure was estimated by measuring total urine arsenic and urine arsenic species using inductively coupled plasma mass spectrometry (ICPMS) and high-performance liquid chromatography-ICPMS, respectively. Urine albumin was measured by automated nephelometric immunochemistry. RESULTS: The prevalence of albuminuria (albumin-creatinine ratio ≥30 mg/g) was 30%. Median value for the sum of inorganic and methylated arsenic species was 9.7 (IQR, 5.8-15.6) μg per gram of creatinine. Multivariable-adjusted prevalence ratios of albuminuria (albumin-creatinine ratio ≥30 mg/g) comparing the 3 highest to lowest quartiles of the sum of inorganic and methylated arsenic species were 1.16 (95% CI, 1.00-1.34), 1.24 (95% CI, 1.07-1.43), and 1.55 (95% CI, 1.35-1.78), respectively (P for trend <0.001). The association between urine arsenic and albuminuria was observed across all participant subgroups evaluated and was evident for both micro- and macroalbuminuria. LIMITATIONS: The cross-sectional design cannot rule out reverse causation. CONCLUSIONS: Increasing urine arsenic concentrations were cross-sectionally associated with increased albuminuria in a rural US population with a high burden of diabetes and obesity. Prospective epidemiologic and mechanistic evidence is needed to understand the role of arsenic as a kidney disease risk factor.
American Journal of Kidney Diseases 11/2012; · 5.43 Impact Factor
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American Journal of Kidney Diseases 10/2012; 60(4):503-6. · 5.43 Impact Factor
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Rebecca Shelley,
Nam-Soo Kim,
Patrick Parsons,
Byung-Kook Lee,
Bernard Jaar,
Jeffrey Fadrowski,
Jacqueline Agnew,
Genevieve M Matanoski,
Brian S Schwartz,
Amy Steuerwald,
Andrew Todd,
David Simon, Virginia M Weaver
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ABSTRACT: Environmental exposure to multiple metals is common. A number of metals cause nephrotoxicity with acute and/or chronic exposure. However, few epidemiologic studies have examined the impact of metal coexposure on kidney function. Therefore, the authors evaluated associations of antimony and thallium with kidney outcomes and assessed the impact of cadmium exposure on those associations in lead workers.
Multiple linear regression was used to examine associations between ln-urine thallium, antimony and cadmium levels with serum creatinine- and cystatin-C-based glomerular filtration measures and ln-urine N-acetyl-β-D-glucosaminidase (NAG).
In 684 participants, median urine thallium and antimony were 0.39 and 0.36 μg/g creatinine, respectively. After adjustment for lead dose, urine creatinine and kidney risk factors, higher ln-urine thallium was associated with higher serum creatinine- and cystatin-C-based estimates of glomerular filtration rate; associations remained significant after adjustment for antimony and cadmium (regression coefficient for serum creatinine-based estimates of glomerular filtration rate =5.2 ml/min/1.73 m(2); 95% CI =2.4 to 8.0). Antimony associations with kidney outcomes were attenuated by thallium and cadmium adjustment; thallium and antimony associations with NAG were attenuated by cadmium.
Urine thallium levels were significantly associated with both serum creatinine- and cystatin-C-based glomerular filtration measures in a direction opposite that expected with nephrotoxicity. Given similarities to associations recently observed with cadmium, these results suggest that interpretation of urine metal values, at exposure levels currently present in the environment, may be more complex than previously appreciated. These results also support multiple metal analysis approaches to decrease the potential for inaccurate risk conclusions.
Occupational and environmental medicine 07/2012; 69(10):727-35. · 3.64 Impact Factor
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Occupational and environmental medicine 03/2012; · 3.64 Impact Factor
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Virginia M Weaver,
Nam-Soo Kim,
Byung-Kook Lee,
Patrick J Parsons,
June Spector,
Jeffrey Fadrowski,
Bernard G Jaar,
Amy J Steuerwald,
Andrew C Todd,
David Simon,
Brian S Schwartz
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ABSTRACT: Cadmium is a well-known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) μg/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The eGFR measures were moderately correlated (rs=0.5; p<0.001). After adjustment, ln (urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln (urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient=4.1 mL/min/1.73 m2; 95% confidence interval=1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential.
Environmental Research 08/2011; 111(8):1236-42. · 3.40 Impact Factor
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ABSTRACT: We evaluated the relationship between secondhand tobacco smoke (SHS) exposure and blood lead levels in US children and adolescents.
We analyzed data from 6830 participants aged 3-19 years in the National Health and Nutrition Examination Survey (1999-2004) who were not active smokers and for whom SHS exposure information and blood lead measurements were available.
After multivariable adjustment, participants in the highest quartile of serum cotinine (≥ 0.44 μg/L) had 28% (95% confidence interval = 21%, 36%) higher blood lead levels than had those in the lowest quartile (< 0.03 μg/L). Similarly, blood lead levels were 14% and 24% higher in children who lived with 1 or with 2 or more smokers, respectively, than they were in children living with no smokers. Among participants for whom lead dust information was available, the associations between SHS and blood lead levels were similar before and after adjustment for lead dust concentrations.
SHS may contribute to increased blood lead levels in US children. Lead dust does not appear to mediate this association, suggesting inhalation as a major pathway of exposure. Eliminating SHS exposure could reduce lead exposure in children.
American Journal of Public Health 08/2011; 102(4):714-22. · 3.93 Impact Factor
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ABSTRACT: Cadmium is a nephrotoxicant at high exposure levels. Few studies have evaluated the role of cadmium in kidney function at low-exposure levels.
We evaluated the association of blood cadmium with estimated glomerular filtration rate (eGFR) in the Korean adult population.
We evaluated 1,909 adults ≥ 20 years of age who participated in the 2005 Korean National Health and Nutrition Examination Survey and had blood cadmium determinations. eGFR was calculated using the Modification of Diet in Renal Disease equation.
Blood cadmium geometric means were 1.57 μg/L for men and 1.49 μg/L for women. The difference in eGFR levels that compared participants in the highest versus lowest cadmium tertiles, after multivariable adjustment, was -1.85 [95% confidence interval (CI): -3.55, -0.16] mL/min per 1.73 m2 in women and 0.67 (-1.16, 2.50) mL/min per 1.73 m2 in men. Among men, the association between blood cadmium and eGFR was modified by blood lead levels (p-value for interaction = 0.048). The fully adjusted differences in eGFR levels for a 2-fold increase in blood cadmium levels were -1.14 (-3.35, 1.07) and 1.84 (0.54, 3.14) mL/min per 1.73 m2 in men with blood lead levels below and above the median (2.75 μg/dL), respectively.
Elevated blood cadmium levels were associated with lower eGFR in women, which supports the role of cadmium as a risk factor for chronic kidney disease. In men, there was no overall association, although elevated blood cadmium levels were associated with higher eGFR levels in men with high blood lead levels and nonstatistically associated with lower eGFR levels in men with low blood lead levels.
Environmental Health Perspectives 08/2011; 119(12):1800-5. · 7.04 Impact Factor
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ABSTRACT: Low-level lead exposure is widespread and has been implicated as a chronic kidney disease (CKD) risk factor. However, studies evaluating associations of lead dose with newer, potentially more accurate, estimates of kidney function, in participants with a wide range of glomerular filtration rates (GFRs), are scarce.
We compared associations of blood lead and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and cystatin C single variable, multivariable and combined creatinine/cystatin C equations in 3941 adults who participated in the 1999-2002 National Health and Nutrition Examination Survey cystatin C subsample.
Geometric mean blood lead was 1.7 μg/dL. After multivariable adjustment, differences [95% confidence interval (CI)] in mean eGFR for a doubling of blood lead were -1.9 (-3.2, -0.7), -1.7 (-3.0, -0.5) and -1.4 (-2.3, -0.5) mL/min/1.73 m(2), using the cystatin C single variable, multivariable and combined creatinine/cystatin C equations, respectively, reflecting lower eGFR with increased blood lead. The corresponding differences (95% CI) were -0.9 (-1.9, 0.02) and -0.9 (-1.8, 0.01) using the creatinine-based MDRD and CKD-EPI equations, respectively. In participants aged ≥60 years, differences in mean eGFR ranged from -3.0 to -4.5 mL/min/1.73 m(2), and odds of reduced eGFR (<60 mL/min/1.73 m(2)) were increased for all estimates of GFR.
These results support the inclusion of cystatin C-based eGFR in future lead research and provide additional evidence for environmental lead exposure as a CKD risk factor.
Nephrology Dialysis Transplantation 01/2011; 26(9):2786-92. · 3.40 Impact Factor
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ABSTRACT: Low-level cadmium exposure, resulting in, for example, urinary cadmium <2.0 μg/g creatinine, is widespread; recent data suggest nephrotoxicity even at these low levels. Few studies have examined the impact of low-level cadmium exposure in workers who are occupationally exposed to other nephrotoxicants such as lead.
We evaluated associations of urine cadmium, a measure of cumulative dose, with four glomerular filtration measures and N-acetyl-β-D-glucosaminidase (NAG) in lead workers. Recent and cumulative lead doses were assessed via blood and tibia lead, respectively.
In 712 lead workers, mean (SD) blood and tibia lead values, urine cadmium values and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation were 23.1 (14.1) μg/dl, 26.6 (28.9) μg Pb/g bone mineral, 1.15 (0.66) μg/g creatinine and 97.4 (19.2) ml/min/1.73 m(2), respectively. After adjustment for age, sex, body mass index, urine creatinine, smoking, alcohol, education, annual income, diastolic blood pressure, current or former lead worker job status, new or returning study participant, and blood and tibia lead, higher ln-urine cadmium was associated with higher calculated creatinine clearance, eGFR (β = 8.7 ml/min/1.73 m(2); 95% CI 5.4 to 12.1) and ln-NAG but lower serum creatinine.
Potential explanations for these results include a normal physiological response in which urine cadmium levels reflect renal filtration, the impact of adjustment for urine dilution with creatinine in models of kidney outcomes, and cadmium-related hyperfiltration.
Occupational and environmental medicine 10/2010; 68(4):250-6. · 3.64 Impact Factor
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ABSTRACT: Chronic, high-level lead exposure is a known risk factor for kidney disease. The effect of current low-level environmental lead exposure is less well known, particularly among children, a population generally free from kidney disease risk factors such as hypertension and diabetes mellitus. Therefore, in this study, we investigated the association between lead exposure and kidney function in a representative sample of US adolescents.
Participants included 769 adolescents aged 12 to 20 years for whom whole blood lead and serum cystatin C were measured in the Third National Health and Nutrition Examination Survey, conducted from 1988-1994. The association between blood lead level and level of kidney function (glomerular filtration rate [GFR]), determined by cystatin C-based and creatinine-based estimating equations, was examined.
Median whole blood lead level was 1.5 microg/dL (to convert to micromoles per liter, multiply by 0.0483), and median cystatin C-estimated GFR was 112.9 mL/min/1.73 m(2). Participants with lead levels in the highest quartile (> or =3.0 microg/dL) had 6.6 mL/min/1.73 m(2)-lower estimated GFR (95% confidence interval, -0.7 to -12.6 mL/min/1.73 m(2)) compared with those in the first quartile (<1 microg/dL). A doubling of blood lead level was associated with a 2.9 mL/min/1.73 m(2)-lower estimated GFR (95% confidence interval, -0.7 to -5.0 mL/min/1.73 m(2)). Lead levels were also associated with lower creatinine-based estimated GFR levels, but the association was weaker than with cystatin C-based GFR and not statistically significant.
Higher blood lead levels in a range below the current Centers for Disease Control and Prevention-designated level of concern (10 microg/dL) were associated with lower estimated GFRs in a representative sample of US adolescents. This finding contributes to the increasing epidemiologic evidence indicating an adverse effect of low-level environmental lead exposure.
Archives of internal medicine 01/2010; 170(1):75-82. · 11.46 Impact Factor
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ABSTRACT: Existing research on the lead dose range associated with nephrotoxicity in the occupational setting is inconsistent and primarily cross-sectional in design.
To determine if lead dose predicts change in renal function in a large population of current and former lead workers.
Three evaluations were performed between 1997 and 2001. Lead dose was assessed with blood and tibia lead. Renal outcomes included blood urea nitrogen, serum creatinine, and calculated creatinine clearance. We used generalized estimating equations to model change in renal function between each evaluation in relation to tibia lead at the beginning of each follow-up period and concurrent change in blood lead, while adjusting for baseline lead dose and other covariates.
At baseline, mean (SD) age and duration of occupational lead exposure were 42.0 (9.3) and 8.8 (6.3) years, respectively, in 537 current and former lead workers followed over a mean of 2.1 years. Mean (SD) blood and tibia lead were 31.3 (14.4) microg/dl and 35.0 (37.8) microg/g bone mineral, respectively. Women (25.9%) were older and more likely to be former lead workers than men. In males, serum creatinine decreased and calculated creatinine clearance increased over the course of the study. Mean blood lead was not significantly different between evaluations 1 and 3 in either sex, however, tibia lead decreased in women. Blood and tibia lead were significantly associated with change in renal function. In males, serum creatinine decreases and calculated creatinine clearance increases were greatest in participants whose blood lead declined.
Both acute and chronic occupational lead dose measures were associated with change in renal function measures prospectively.
Environmental Research 12/2008; 109(1):101-7. · 3.40 Impact Factor
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ABSTRACT: To compare associations of patella lead, a lead pool that may capture aspects of both current bioavailable and cumulative lead dose thus offering advantages over tibia or blood lead, with blood lead in models of blood pressure and hypertension and to examine effect modification by age, sex and polymorphisms of the genes encoding for the vitamin D receptor (VDR) and delta-aminolevulinic acid dehydratase (ALAD).
Cross-sectional data in 652 current and former lead workers were analyzed.
Blood lead, but not patella lead, was positively associated with systolic blood pressure. Neither lead measure was associated with diastolic blood pressure or hypertension status. There was no evidence of effect modification.
In these workers, blood lead was more relevant to elevations in blood pressure than was patella lead. Additional research will be required to determine whether patella lead assessment provides unique information on vascular risk from lead exposure.
American Journal of Industrial Medicine 06/2008; 51(5):336-43. · 1.63 Impact Factor
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MPH Virginia M. Weaver MD,
MPH Lenworth R. Ellis MD,
DrMSc Byung-Kook Lee MD,
Andrew C. Todd PhD,
MS Weiping Shi MD,
DrPH Kyu-Dong Ahn MPH,
MS Brian S. Schwartz MD, Virginia M. Weaver,
Lenworth R. Ellis,
Byung‐Kook Lee,
Andrew C. Todd,
Weiping Shi,
Kyu‐Dong Ahn,
Brian S. Schwartz
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ABSTRACT: Background
To compare associations of patella lead, a lead pool that may capture aspects of both current bioavailable and cumulative lead dose thus offering advantages over tibia or blood lead, with blood lead in models of blood pressure and hypertension and to examine effect modification by age, sex and polymorphisms of the genes encoding for the vitamin D receptor (VDR) and δ-aminolevulinic acid dehydratase (ALAD).Methods
Cross-sectional data in 652 current and former lead workers were analyzed.ResultsBlood lead, but not patella lead, was positively associated with systolic blood pressure. Neither lead measure was associated with diastolic blood pressure or hypertension status. There was no evidence of effect modification.Conclusions
In these workers, blood lead was more relevant to elevations in blood pressure than was patella lead. Additional research will be required to determine whether patella lead assessment provides unique information on vascular risk from lead exposure. Am. J. Ind. Med. 51:336–343, 2008. © 2008 Wiley-Liss, Inc.
American Journal of Industrial Medicine 04/2008; 51(5):336 - 343. · 1.63 Impact Factor
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Occupational and environmental medicine 04/2007; 64(3):141-2. · 3.64 Impact Factor
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ABSTRACT: Several studies have examined longitudinal associations of blood pressure change or hypertension incidence with lead concentration in blood or bone. It is not clear whether the observed associations reflect an immediate response to lead as a consequence of recent dose or rather are a persistent effect of cumulative dose over a lifetime.
We followed 575 subjects in a lead-exposed occupational cohort in South Korea between October 1997 and June 2001. We used generalized estimating equation models to evaluate blood pressure change between study visits in relation to tibia lead concentrations at each prior visit and concurrent changes in blood lead. The modeling strategy summarized the longitudinal association of blood pressure with cumulative lead dose or changes in recent lead dose.
On average, participants were 41 years old at baseline and had worked 8.5 years in lead-exposed jobs. At baseline, the average +/- standard deviation for blood lead was 31.4 +/- 14.2 microg/dL, and for tibia lead, it was 38.4 +/- 42.9 microg/g bone mineral. Change in systolic blood pressure during the study was associated with concurrent blood lead change, with an average annual increase of 0.9 (95% confidence interval = 0.1 to 1.6) mm Hg for every 10-microg/dL increase in blood lead per year.
The findings in this relatively young population of current and former lead workers suggest that systolic blood pressure responds to lead dose through acute pathways in addition to the effects of cumulative injury.
Epidemiology 10/2006; 17(5):538-44. · 5.57 Impact Factor
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Virginia M Weaver,
Byung-Kook Lee,
Andrew C Todd,
Kyu-Dong Ahn,
Weiping Shi,
Bernard G Jaar,
Karl T Kelsey,
Mark E Lustberg,
Ellen K Silbergeld,
Patrick J Parsons,
Jiayu Wen,
Brian S Schwartz
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ABSTRACT: Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.
Environmental Research 10/2006; 102(1):61-9. · 3.40 Impact Factor
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ABSTRACT: Lead exposure in adults is associated with worse cognitive function in cross-sectional and longitudinal studies. Previous studies have mainly examined relations with blood lead or cortical bone lead; few have examined trabecular bone lead.
We performed a cross-sectional analysis of the relations of patella lead and other lead biomarkers with measures of neurobehavioral and peripheral nervous system function in 652 lead workers.
Patella lead was found to be associated with worse performance on seven of 19 tests of manual dexterity, sensory vibration threshold, and depressive symptoms. The associations of patella lead with cognitive function were essentially similar to those with blood lead or tibia lead but of somewhat lower magnitude.
In this study, measurement of patella lead did not aid causal inference regarding cognitive effects when compared with blood lead and tibia lead.
Journal of Occupational and Environmental Medicine 06/2006; 48(5):489-96. · 2.06 Impact Factor
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Virginia M Weaver,
Brian S Schwartz,
Bernard G Jaar,
Kyu-Dong Ahn,
Andrew C Todd,
Sung-Soo Lee,
Karl T Kelsey,
Ellen K Silbergeld,
Mark E Lustberg,
Patrick J Parsons,
Jiayu Wen,
Byung-Kook Lee
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ABSTRACT: Recent research suggests that uric acid may be nephrotoxic at lower levels than previously recognized and that it may be one mechanism for lead-related nephrotoxicity. Therefore, in understanding mechanisms for lead-related nephrotoxicity, it would be of value to determine whether genetic polymorphisms that are associated with renal outcomes in lead workers and/or modify associations between lead dose and renal function are also associated with uric acid and/or modify associations between lead dose and uric acid. We analyzed data on three such genetic polymorphisms: delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR). Mean (+/- SD) tibia, blood, and dimercaptosuccinic acid-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0+/- 15.0 g/dL, and 0.77+/- 0.86 microg/mg creatinine, respectively, in 798 current and former lead workers. Participants with the eNOSAsp allele had lower mean serum uric acid compared with those with the Glu/Glu genotype. Among older workers (age > or = median of 40.6 years), ALAD genotype modified associations between lead dose and uric acid levels. Higher lead dose was significantly associated with higher uric acid in workers with the ALAD1-1 genotype; associations were in the opposite direction in participants with the variant ALAD1-2 genotype. In contrast, higher tibia lead was associated with higher uric acid in those with the variant VDRB allele; however, modification was dependent on participants with the bb genotype and high tibia lead levels. We conclude that genetic polymorphisms may modify uric acid mediation of lead-related adverse renal effects.
Environmental Health Perspectives 11/2005; 113(11):1509-15. · 7.04 Impact Factor
