Associations of Community Water Lead Concentrations with Hemoglobin Concentrations and Erythropoietin-Stimulating Agent Use among Patients with Advanced CKD

Abstract

Background: Although patients with kidney disease may be particularly susceptible to the adverse health effects associated with lead exposure, whether levels of lead found commonly in drinking water are associated with adverse outcomes in patients with ESKD is not known.

Methods: To investigate associations of lead in community water systems with hemoglobin concentrations and erythropoietin stimulating agent (ESA) use among incident patients with ESKD, we merged data from the Environmental Protection Agency (EPA) Safe Drinking Water Information System (documenting average 90^th percentile lead concentrations in community water systems during 5 years before dialysis initiation, according to city of residence) with patient-level data from the United States Renal Data System.

Results: Among 597,968 patients initiating dialysis in the United States in 2005 through 2017, those in cities with detectable lead levels in community water had significantly lower pre-ESKD hemoglobin concentrations and more ESA use per 0.01 mg/L increase in 90^th percentile water lead. Findings were similar for the 208,912 patients with data from the first month of ESKD therapy, with lower hemoglobin and higher ESA use per 0.01 mg/L higher lead concentration. These associations were observed at lead levels below the EPA threshold (0.015 mg/L) that mandates regulatory action. We also observed environmental inequities, finding significantly higher water lead levels and slower declines over time among Black versus White patients.

Conclusions: This first nationwide analysis linking EPA water supply records to patient data shows that even low levels of lead that are commonly encountered in community water systems throughout the United States are associated with lower hemoglobin levels and higher ESA use among patients with advanced kidney disease.

Keywords: anemia; disparities; environmental risk factors; lead toxicity; racial and ethnic disparities.

Graphical abstract

Figure 1.

Cubic polynomials were fitted to illustrate the adjusted difference in pre-ESKD hemoglobin concentration, according to the 90^th percentile community water lead concentration in the patient’s city of primary residence. To account for the effect of ESA treatment, corrected hemoglobin was derived by subtracting 2 g/dl from observed hemoglobin concentration among pre-ESKD ESA users. Adjusted for age, sex, race, history of diabetes, congestive heart failure, hypertension, cancer, tobacco use, body mass index, estimated glomerular function, insurance status, employment, year of dialysis initiation, and county air pollution. Dashed lines reflect 95% CI. The figure excludes patients (n=3187) in cities with a reported lead concentration ≥0.03 mg/L.

Figure 2.

Cubic polynomials were fitted to illustrate the adjusted difference in ESA use before dialysis initiation, according to the 90^th percentile community water lead concentration in a patient’s city of primary residence. Adjusted for age, sex, race, history of diabetes, congestive heart failure, hypertension, cancer, tobacco use, body mass index, estimated glomerular function, insurance status, employment, year of dialysis initiation, and county air pollution. Dashed lines reflect 95% CI. The figure excludes patients in cities with lead concentrations ≥0.03 mg/L.

Figure 3.

Temporal trends in the mean (95% CI) 90^th percentile community water lead concentrations for Black and White patients with ESKD were significantly different (P<0.001). The adjusted per calendar year change in lead levels was 0.0002 mg/L lower per year among White patients, compared with 0.0001 mg/L lower per year among Black patients.