World Trade Center Kidney-Link

• ClinicalTrials.gov Identifier: NCT03234530
• Recruitment Status: Completed
• First Posted: July 31, 2017
• Last Update Posted: June 9, 2021
• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health (NIOSH/CDC)
• Information provided by (Responsible Party): Maryann Mclaughlin, Icahn School of Medicine at Mount Sinai

Study Description

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.

Condition or disease
Chronic Kidney Diseases; Obstructive Sleep Apnea

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 555 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Linking the Effects of 9/11 to Kidney Disease
• Actual Study Start Date: November 1, 2017
• Actual Primary Completion Date: June 1, 2021
• Actual Study Completion Date: June 1, 2021

Groups and Cohorts

Group/Cohort
WTC responders; WTC Health Program participants
Urban workers; Control group of urban workers in NYC not exposed to the dust from the WTC

Outcome Measures

Primary Outcome Measures :

1. glomerular filtration rate (eGFR) [ Time Frame: day 1 ]
   eGFR will be calculated using the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equations. The proposed studies will evaluate differences in the combined creatinine-cystatin C eGFR, which provides the most accurate estimate of GFR, and the creatinine-based CKD-EPI eGFR, which is more practical for use in clinical practice and in monitoring programs. Values > 200 will be set to 200mL/min/1.73m2
2. albuminuria [ Time Frame: day 1 ]
   albumin level in urine

Secondary Outcome Measures :

1. Berlin questionnaire [ Time Frame: day 1 ]
   Those who are not diagnosed with sleep apnea will be assessed for risk of developing sleep apnea using the Berlin questionnaire. It includes 11 questions organized into three categories, 5 questions related to snoring and the cessation of breathing in category 1, 4 questions related to daytime sleepiness in category 2, 1 question about high blood pressure, and 1 question regarding BMI in category 3. When two of three categories are classified as positive for a patient, the patient is rated as being at high risk of having OSA.
2. apnea-hypopnea index (AHI) [ Time Frame: day 1 ]

   Those at high risk for sleep apnea will undergo home sleep a study test to determine apnea hypopnea index (AHI).

   Those diagnosed with sleep apnea, latest sleep study will be used to obtain AHI. To determine AHI, add the total number of apnea events, plus hypopnea events and divide by the total number of minutes of actual sleep time, then multiply by 60. AHI - Apnea Hypopnea Index - The # of apneas and hypopneas per hour.

Biospecimen Retention:   Samples Without DNA

Serum, plasma, urine

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

World Trade Center rescue and recovery workers and volunteers who are enrolled or being seen in any WTC Clinical Centers of Excellence

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

Contacts and Locations

Locations

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai

Centers for Disease Control and Prevention

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

Investigators

• Principal Investigator: Mary Ann McLaughlin, MD, MPH; Icahn School of Medicine at Mount Sinai

More Information

• Responsible Party: Maryann Mclaughlin, Associate Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT03234530
• Other Study ID Numbers: GCO 16-0899; U01OH011326-01A1 ( U.S. NIH Grant/Contract )
• First Posted: July 31, 2017
• Last Update Posted: June 9, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The final research data will be a computerized dataset and includes self-reported demographic and medical data, responses from standard questionnaires, as well as results of laboratory tests (urine and blood samples) . Even though the final dataset will be stripped of identifiers prior to release for sharing, we believe that there remains the possibility of deductive disclosure of subjects with unusual characteristics. Thus, we will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maryann Mclaughlin, Icahn School of Medicine at Mount Sinai:

albuminuria; sleep apnea; particulate matter; renal injury

Additional relevant MeSH terms:

Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Renal Insufficiency