World Trade Center Kidney-Link

NCT ID: NCT03234530

Last Updated: 2021-06-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 555 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-11-01
• Study Completion Date: 2021-06-01

Brief Summary

This study focuses on the prevalence and identification of kidney disease among participants of the WTC Health Program and the study team are planning to assess kidney disease in a multi-factorial manner. The first aim of this study is to correlate kidney dysfunction with 9/11 exposure, and the study team predicts that exposure to 9/11 is an independent risk factor in kidney disease among the WTC Health Program participants. Secondly, the study team proposes that a well-established WTC-related condition, obstructive sleep apnea (OSA), is independently associated with kidney disease. In addition, the study team believe there is a temporal causative relationship between evidence of kidney disease and the severity of OSA. Finally, the last aim is to further identify and explore potential mechanisms and phenotypes of kidney disease in participants of the WTC Health Programs.

Regardless of whether the analyses support or reject these hypotheses, the findings will be of equally great public health importance. Successful completion of the proposed research would address a critical knowledge gap regarding the risk of kidney damage among this group of patients, and would inform future mechanistic studies with the potential to impact prevention.

Detailed Description

Exposure to environmental toxins results in significant long-term health effects in workers. More than 91,000 rescue and recovery workers and volunteers at the World Trade Center (WTC) sustained exposure to thousands of tons of coarse and fine particulate matter. Thousands of responders are currently treated for WTC-related health conditions or may be at risk for worsening health. Toxic effects of particulate matter are known to affect the pulmonary, renal and cardiovascular systems. The specific effects of the exposure to 9/11 are partly known, and require further investigation, as outlined in the Zadroga Act (Public Law111-347).

This study builds on the preliminary data to address a critical knowledge gap about the risk of kidney damage among WTC responders, the progression of kidney decline since exposure, and the association of kidney disease with a defined WTC-related diagnosis, obstructive sleep apnea (OSA). Successful completion of the proposed research would address a critical knowledge gap regarding the risk of kidney damage and the relationship to important chronic diseases (OSA and immune-mediated disease) among WTC participants, and would inform future mechanistic studies with the potential to impact disease prevention.

Specific Aim 1: To quantify the risk of kidney damage and the relationship to 9/11 exposure among WTC Health Program participants. Currently, the cohort of 406 first responders represents the sole dedicated evaluation of kidney disease in WTC Health Program participants. The study team will test the hypothesis that exposure to 9/11 is independently associated with kidney disease and enrich the enrollment of the current study population with a diversified population including categories of workers who have not been enrolled, as well as a control group of urban workers (NYC) not exposed to the dust from the WTC.

Aim 1a. The study team hypothesize that albuminuria and decreased estimated glomerular filtration rate (eGFR) will occur more frequently in WTC responders than in the general population and will correlate with the degree of exposure as defined by the previously defined WTC exposure score (adjusting for demographics, family history of chronic kidney disease (CKD), and diagnosed, treated or laboratory confirmed diabetes and hypertension). The study team will also assess established urine biomarkers of proximal tubular injury, including β2-M, Kidney Injury Molecule-1 (KIM-1), and Interleukin 18 (IL-18), as well as markers of distal tubular function, Loop of Henle function, and tubulointerstitial inflammation.

Aim 1b. The study team hypothesize that initial exposure to 9/11 contributed to reduction in renal function over time. The study team will quantify change in renal function over time by analyzing eGFR at WTC Health Program Visit 1 (V1) and subsequent visits, adjusting for known co-morbid conditions.

Aim 1c. The study team will create a repository of WTC responders with established kidney disease (including relatively rare disease) to qualitatively evaluate and describe the spectrum of kidney disease in the entire WTC population and compare to patterns of kidney disease in the general population. The study team will actively enlist those with a verified physician diagnosis of kidney disease, and collect biopsy reports and slides for review.

Specific Aim 2: Evaluate the association of kidney disease and the established WTC-related condition, OSA.

Aim 2a. OSA is particularly prevalent among WTC cohorts. The study team hypothesize that there is an independent association between prevalent OSA and prevalent kidney disease.

Aim2b. The study team hypothesize that OSA independently contributes to the progression of kidney disease. The study team will assess the temporal relationship of eGFR decline to the presence and severity of OSA, using longitudinal data from the WTC data center.

Specific Aim 3: To evaluate potential mechanisms of kidney injury in WTC Health Program participants.

Aim3a. In order to understand the role of chronic inflammation, the study team will evaluate established inflammatory markers which have been implicated as potential mediators of both OSA and CKD, including IL-10, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, IL-12p70., high sensitivity C-reactive protein (hs-CRP), and white blood cell count (WBC).

Aim3b. Based on the preliminary data noting increases in heavy metal levels in urine and blood, the study team will narrow the focus to evaluate the role of cadmium and lead in the development of kidney disease with evaluations of lead content in bone (marker of long-term exposure) as well as in blood. Since study participants include law enforcement personnel (with known exposure to lead), the characterization of bone lead levels will have an important health impact, whether or not a relationship to 9/11 is detected.

Aim3c. In a registry cohort of WTC responders with established kidney disease the study team will explore potential mechanisms as determined by the observed patterns of disease by developing a comprehensive repository of data on WTC Health Program participants with common and rare kidney diseases, the study team will define specific clinical profiles and identify potential mechanisms that warrant future study. Importantly, the study team will develop a process across all WTC Health Programs (inclusive of approximately 50,000 individuals), to monitor those with early kidney disease as well as those with biopsy-proven kidney disease, at any stage.

Conditions

Chronic Kidney Diseases; Obstructive Sleep Apnea

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

WTC responders

WTC Health Program participants

No interventions assigned to this group

Urban workers

Control group of urban workers in NYC not exposed to the dust from the WTC

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Exposed Group: - Adult patients (35 to 75 years)

• Enrolled or was seen at any of the WTC Clinical Centers of Excellence

Unexposed Group: - Adult patients (35 to 75 years)

• Lived or worked in NYC at least 10 years since 9/11/01 but were not exposed to the the dust at Ground Zero (not living in proximity of Ground Zero, nor involved in the rescue and recovery at Ground Zero

Registry Part: - Adult patient (18 to 75 years)

• Enrolled or was seen at any of the WTC Clinical Centers of Excellence or WTC Environmental Health Centers
• With a diagnosis of any Kidney Injury or disease after 9/11/01

Exclusion Criteria

• Patients below 18 years of age
• Individuals with an occupation involving chronic exposure to inhaled particulate matter (e.g. iron/steel workers and sand hog workers)
• For the registry part, patients with kidney disease prior to 9/11/01

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

National Institute for Occupational Safety and Health (NIOSH/CDC)

FED

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Maryann Mclaughlin

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary Ann McLaughlin, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

Other Identifiers

U01OH011326-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 16-0899

Identifier Type: -

Identifier Source: org_study_id