Environmental & Genetic Risk Factors for Renal Function

Summary

Principal Investigator: V M Weaver
Abstract: DESCRIPTION (provided by applicant): End stage renal disease (ESRD) is associated with substantial morbidity and mortality. Strategies to prevent the renal function decline that can ultimately result in ESRD are essential. The impact of environmental exposures has received relatively little attention in this regard, despite the fact that exposures such as cadmium and lead are known renal toxicants that are stored long-term in the body and ubiquitous in humans. In fact, the lead and cadmium dose-effect curves for renal function remain uncertain for the low to moderate range of doses. The proposed study will investigate a broad set of causes of renal function decline, including lead, cadmium, blood pressure, diabetes, nephrotoxic medication use, genetic polymorphisms, and age. This application is a competing renewal application of the study "Exposure, dose, body burden, and health effects of lead" (Schwartz BS, PI) conducted from 1997-2001. It will build on data, from the large cohort of current and former lead workers and participants without occupational lead exposure in the originally funded grant. Study subjects have a wide range of lead exposure and dose measures and renal outcome data from three visits each over an average of 2.2 years. Analysis of existing data has already provided very important results, including longitudinal decline in renal function associated with lead dose measures;interaction between age and lead dose on renal function and renal function decline;interaction between ALAD genotype and lead dose on renal function;and associations of environmental level cadmium dose with elevated NAG in a subset of lead workers. However, in order to better understand the causes of renal function decline, cadmium dose must be characterized in all subjects, additional genotypes must be measured, and additional follow-up time is needed because of the slow rate of renal function decline. We propose to include 675 participants from the first study and enroll 225 new current or former lead workers over age 45 years, those at greater risk for renal function decline. We will obtain blood and tibia lead, genotyping, urinary cadmium, BUN, serum creatinine, measured and calculated creatinine clearances, NAG and RBP during 3 evaluations at yearly intervals. The specific aims are to determine: 1) if lead and cadmium dose are or continue to be associated with renal function at cross-section and longitudinally;2) if there is effect modification by lead or cadmium dose, respectively, on associations between cadmium or lead dose and renal function decline;3) if hypertension modifies the relations of lead or cadmium dose with renal function decline;and 4) whether polymorphisms in the genes for ALAD, VDR, ACE, and eNOS modify or continue to modify relations of lead and/or cadmium dose with renal outcomes. We believe the proposed work will allow a more complete understanding of the causes of renal function decline and lead to the development of public health interventions to prevent this considerable public health problem.
Funding Period: 2009-09-06 - 2010-05-31
more information: NIH RePORT

Top Publications

  1. ncbi Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers
    Virginia M Weaver
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Environ Res 102:61-9. 2006
  2. pmc Associations of multiple metals with kidney outcomes in lead workers
    Rebecca Shelley
    Division of Occupational and Environmental Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Rm 7041, Baltimore, MD 21205, USA
    Occup Environ Med 69:727-35. 2012
  3. ncbi Uranium associations with kidney outcomes vary by urine concentration adjustment method
    Rebecca Shelley
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
    J Expo Sci Environ Epidemiol 24:58-64. 2014
  4. ncbi Comparison of patella lead with blood lead and tibia lead and their associations with neurobehavioral test scores
    Carrie D Dorsey
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
    J Occup Environ Med 48:489-96. 2006
  5. ncbi Changes in systolic blood pressure associated with lead in blood and bone
    Barbara S Glenn
    Office of Research and Development, U S Environmental Protection Agency, 1600 Pennsylvania Avenue, Washington, DC 20460, USA
    Epidemiology 17:538-44. 2006
  6. pmc Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C
    Virginia M Weaver
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615N Wolfe St, Rm 7041, Baltimore, MD 21205, USA
    Environ Res 111:1236-42. 2011
  7. pmc Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations
    June T Spector
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
    Nephrol Dial Transplant 26:2786-92. 2011
  8. pmc Associations of low-level urine cadmium with kidney function in lead workers
    Virginia M Weaver
    Division of Occupational and Environmental Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Rm 7041, Baltimore, MD 21205, USA
    Occup Environ Med 68:250-6. 2011
  9. pmc Cadmium and peripheral arterial disease: gender differences in the 1999-2004 US National Health and Nutrition Examination Survey
    Maria Tellez-Plaza
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Am J Epidemiol 172:671-81. 2010
  10. ncbi Lead-related nephrotoxicity: a review of the epidemiologic evidence
    E B Ekong
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Kidney Int 70:2074-84. 2006

Scientific Experts

  • V M Weaver
  • B S Schwartz
  • Rebecca Shelley
  • Ana Navas-Acien
  • Byung Kook Lee
  • Jeffrey Fadrowski
  • Bernard Jaar
  • Eliseo Guallar
  • Maria Tellez-Plaza
  • Andrew C Todd
  • Nam Soo Kim
  • Jacqueline Agnew
  • David Simon
  • June T Spector
  • Regina A Shih
  • Carrie D Dorsey
  • E B Ekong
  • Barbara S Glenn
  • Amy J Steuerwald
  • Bernard G Jaar
  • Patrick J Parsons
  • Genevieve Matanoski
  • Andrew Todd
  • Amy Steuerwald
  • Patrick Parsons
  • Genevieve M Matanoski
  • Ciprian M Crainiceanu
  • A Richey Sharrett
  • Ellen Silbergeld
  • Paul Muntner
  • Howard Hu
  • Marc G Weisskopf
  • Karen Bandeen-Roche
  • Karen I Bolla
  • B G Jaar
  • Gap Soo Lee
  • Sung Soo Lee
  • Weiping Shi

Detail Information

Publications16

  1. ncbi Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers
    Virginia M Weaver
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Environ Res 102:61-9. 2006
    ..In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes...
  2. pmc Associations of multiple metals with kidney outcomes in lead workers
    Rebecca Shelley
    Division of Occupational and Environmental Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Rm 7041, Baltimore, MD 21205, USA
    Occup Environ Med 69:727-35. 2012
    ..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...
  3. ncbi Uranium associations with kidney outcomes vary by urine concentration adjustment method
    Rebecca Shelley
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
    J Expo Sci Environ Epidemiol 24:58-64. 2014
    ..These findings support consideration of non-creatinine-based methods of adjustment for urine concentration in nephrotoxicant research...
  4. ncbi Comparison of patella lead with blood lead and tibia lead and their associations with neurobehavioral test scores
    Carrie D Dorsey
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
    J Occup Environ Med 48:489-96. 2006
    ..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...
  5. ncbi Changes in systolic blood pressure associated with lead in blood and bone
    Barbara S Glenn
    Office of Research and Development, U S Environmental Protection Agency, 1600 Pennsylvania Avenue, Washington, DC 20460, USA
    Epidemiology 17:538-44. 2006
    ..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...
  6. pmc Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C
    Virginia M Weaver
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615N Wolfe St, Rm 7041, Baltimore, MD 21205, USA
    Environ Res 111:1236-42. 2011
    ..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...
  7. pmc Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations
    June T Spector
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
    Nephrol Dial Transplant 26:2786-92. 2011
    ..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...
  8. pmc Associations of low-level urine cadmium with kidney function in lead workers
    Virginia M Weaver
    Division of Occupational and Environmental Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Rm 7041, Baltimore, MD 21205, USA
    Occup Environ Med 68:250-6. 2011
    ..Few studies have examined the impact of low-level cadmium exposure in workers who are occupationally exposed to other nephrotoxicants such as lead...
  9. pmc Cadmium and peripheral arterial disease: gender differences in the 1999-2004 US National Health and Nutrition Examination Survey
    Maria Tellez-Plaza
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Am J Epidemiol 172:671-81. 2010
    ..These findings add to the concern of increased cadmium exposure as a cardiovascular risk factor in the general population...
  10. ncbi Lead-related nephrotoxicity: a review of the epidemiologic evidence
    E B Ekong
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Kidney Int 70:2074-84. 2006
    ..Global efforts to reduce lead exposure remain important. Research is also needed to determine whether specific therapies, such as chelation, are beneficial in susceptible populations...
  11. pmc Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis
    Ana Navas-Acien
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Am J Epidemiol 170:1156-64. 2009
    ..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...
  12. ncbi Associations between patella lead and blood pressure in lead workers
    Virginia M Weaver
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Am J Ind Med 51:336-43. 2008
    ....
  13. ncbi Lead and cognitive function in adults: a questions and answers approach to a review of the evidence for cause, treatment, and prevention
    Brian S Schwartz
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
    Int Rev Psychiatry 19:671-92. 2007
    ..The strong and compelling body of literature on lead and cognitive dysfunction and decline also supports a need for intervention studies to prevent lead-related cognitive decline...
  14. pmc Cumulative lead dose and cognitive function in adults: a review of studies that measured both blood lead and bone lead
    Regina A Shih
    Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland 20892, USA
    Environ Health Perspect 115:483-92. 2007
    ..We review empirical evidence for the relations of recent and cumulative lead dose with cognitive function in adults...
  15. pmc Adult lead exposure: time for change
    Brian S Schwartz
    Department of Environmental Health Sciences and Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Environ Health Perspect 115:451-4. 2007
    ..We hope this mini-monograph will motivate renewed discussion of ways to protect lead-exposed adults in the United States and around the world...
  16. pmc Longitudinal associations between lead dose and renal function in lead workers
    Virginia M Weaver
    Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Room 7041, Baltimore, MD 21205, USA
    Environ Res 109:101-7. 2009
    ..Existing research on the lead dose range associated with nephrotoxicity in the occupational setting is inconsistent and primarily cross-sectional in design...