A Large Cohort Linkage Study of Lead Exposure for Mortality & End Stage Renal Disease Pubblico

Chowdhury, Ritam (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/bz60cw42p?locale=it
Published

Abstract

We studied the association of lead exposure with mortality and end-stage renal disease (ESRD) incidence in 58,000 subjects who were part of an occupational lead surveillance in 11 states and had blood lead levels (BLLs) recorded during the period 1982-2005. Subjects were divided into four groups, based on their highest BLL: <5 µg/dl, 5 to <25 µg/dl, 25 to <40 µg/dl, and 40+ µg/dl.

In the first study, we compared the lead-exposed cohort's mortality to the US population, and did internal comparisons of high lead groups compared to low. In the second study, we conducted similar analyses for ESRD incidence. In the third study, we used Cox regression to study risk of mortality after ESRD incidence by lead category.

In the first study, we found evidence of increased risk of lung and larynx cancer with higher lead exposure, with significant positive trends in lung cancer by increasing lead category (test for trend p=0.0001). The SMR for highest blood lead category was 1.2, increasing to 1.35 with 20 years latency. Positive trends were also seen for mortality due to heart disease and kidney disease. Data are limited by a lack of work history and smoking data, different follow-up time for different lead categories, and small numbers of deaths for some causes. In our second study, we found evidence for increased ESRD incidence for those in the highest BL category (51+µg/dl) in this cohort (standardized rate ratio for highest blood lead category, with 5 years latency, 1.59). In our third study, we found no association between blood lead level and survival after ESRD diagnosis.

Table of Contents

CHAPTER 1: INTRODUCTION.. 1
Study Motivation 1
Study Contribution 3
Study Objectives 5
CHAPTER 2. LITERATURE REVIEW... 7
Pathophysiology 8
Review of Epidemiologic Literature by Outcome. 11
1. Cancer 11
2. Blood Pressure 16
3. Stroke (Cerebrovascular Disease) 19
4. Cardiovascular or Heart Disease. 21
5. Nonmalignant Kidney Disease 29
CHAPTER 3. RESEARCH DESIGN AND METHODS. 34
Overall Study Design and Hypotheses of Interest 34
Study Population: Adult Blood Lead Epidemiology and Surveillance (ABLES) Program 35
Analytic Cohort Selection 38
Exposure Data 41
1. Selection Bias 44
2. Misclassification of Exposure 44
3. Blood Lead vs. Bone Lead 45
Outcome Data 48
1. National Death Index 48
2. United States Renal Data System.. 48
Analytic Plan 50
Comparison of Poisson and Cox Proportional Hazards Models. 56
1. Poisson Distribution 56
2. Cox Proportional Hazards Model 58
3. Comparing Poisson to Cox PH Models. 60
CHAPTER 4. Lead exposure and mortality among participants in a lead surveillance program 63
CHAPTER 5. Lead exposure and incident End Stage Renal Disease (ESRD) among participants in a lead surveillance program.. 98
CHAPTER 6. Survival patterns in a cohort of lead exposed workers with End Stage Renal Disease (ESRD) from the Adult Blood Lead Epidemiology & Surveillance (ABLES) program. 126
CHAPTER 7. CONCLUSION.. 151
Lead Exposure and Mortality 151
Lead Exposure and Incident End Stage Renal Disease (ESRD) 152
Lead, ESRD and Survival 153
Strengths 154
Limitations 154
Future Directions 159
APPENDIX 1: LEAD EFFECTS ON THE BODY: PATHOPHYSIOLOGY.. 160
REFERENCES 167

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