Dyspnea Assessment in Hemodialysis Patients

Completed

• Conditions: Dyspnea; Uremic; Hemodialysis-Induced Symptom; Chronic Lung Disease; Chronic Heart Disease; Sodium Excess; End Stage Renal Disease
• Interventions: Diagnostic Test: Lung MRI; Diagnostic Test: Sodium MRI; Diagnostic Test: Chest CT; Diagnostic Test: Echocardiography; Diagnostic Test: Fractional Exhaled Nitric Oxide; Diagnostic Test: Pulmonary Function Tests; Diagnostic Test: Blood Sampling; Diagnostic Test: Six-Minute Walk Test; Diagnostic Test: Dyspnea Questionnaires

• Registration Number: NCT03773991
• Lead Sponsor: Lawson Health Research Institute

Brief Summary

Shortness of breath is very common among patients on dialysis for kidney failure; however, its causes are often not understood. This study will explore the lungs and the heart of these patients to determine the causes of shortness of breath. The amount of salt in the body tissues, which tends to accumulate in dialysis patients and can also cause shortness of breath, will also be measured. Machines that exploit magnetic resonance, ultrasound and x-rays to take images of the body interior will be employed; in addition, breathing tests, questionnaires and blood tests will also be used. 20 patients on dialysis will be recruited and have two visits: one at the beginning of the study and one year later to observe any changes in the lungs, heart and salt accumulation over time.

Detailed Description

Rationale:

The available evidence suggest that End-Stage Renal Disease (ESRD) and hemodialysis (HD) have harmful effects on the lungs; the investigators hypothesize that these recurring pulmonary insults, in an analogous way as recurring myocardial ischemic injury for the heart, cause long term impairment in the pulmonary parenchyma, airways and circulation. In addition, observational studies have reported that dyspnea is a common symptom among ESRD patients on chronic HD treatment; however, no study up to now has directly addressed the issue, so that the relationship between dyspnea and pulmonary involvement in the HD population remains poorly understood.

The aim of this study is to explore the pathophysiological basis of dyspnea in patients with end stage renal disease on chronic HD, by using state-of-the-art imaging and functional study techniques.

Study Design:

This is an exploratory study involving a single center recruiting patients from the prevalent dialysis population of London, Ontario. 20 patients on maintenance hemodialysis will be recruited. The patients will undergo imaging, functional studies and blood sampling at the Robarts Research Institute on a non-dialysis day, during the short interval in the dialysis schedule, at baseline and after one year.

Study Procedures:

Blood Collection: blood will be collected from a venous access for standard-of-care tests, uremia and inflammation biomarkers.

Dyspnea Assessment: dyspnea will be assessed with the following self-administered questionnaires: Modified Medical Research Council Breathlessness Scale, the University of California, San Diego Shortness of Breath Questionnaire Pulmonary Function Tests: spirometry and plethysmography pre and post salbutamol administration, carbon monoxide diffusion (DLCO) and the fractional exhaled nitric oxide (FeNO) will be evaluated.

Six Minute Walk Test: the subjects able to do so will perform a six minute walk test, their dyspnea and overall fatigue at baseline and at the end of the exercise will be evaluated using the Borg Scale.

Lung MRI: a proton MRI with ultrashort echo time (UTE) acquisition sequences for the study of lung parenchyma and lung water will be employed. Images will be acquired twice, both pre and post a bronchodilator (salbutamol) challenge.

Sodium MRI: a proton T1 weighted fast-low-angle-shot (FLASH)- sequence will be acquired to delineate the anatomy of the lower leg. Then, a sodium MRI study of the subjects' legs (\~5 cm below the knee) will be obtained with the custom-made sodium coil at 3.0 Tesla.

Water content will also be quantified using proton-MRI with fat-suppressed inversion recovery sequence with proton density contrast.

Chest CT: a high-resolution chest CT scan will be performed using a 64-slice CT scanner. A low radiation dose protocol will be employed. A qualitative and quantitative evaluation of pulmonary airways, blood vessels and parenchyma will be performed.

2D Transthoracic Echocardiography: images will be taken in the left lateral decubitus. Images and loops from standard parasternal long axis and short axis, subcostal, apical 4, 2 and 3- chamber views will be recorded and analyzed for: global longitudinal strain, left ventricular ejection fraction, left ventricular mass, left atrial volume, right ventricular diameter, right atrial volume, right ventricular wall thickness, tricuspid annular plane systolic excursion, pulmonary artery systolic pressure, E/A ratio, E/E' ratio at the basal interventricular septum, aortic, mitral, tricuspid and pulmonary valve qualitative and quantitative function.

Study Timeline

• Study First Submitted: 2018-11-29
• Study First Submitted QC: 2018-12-10
• Study First Posted: 2018-12-12
• Study Start: 2019-03-29
• Primary Completion: 2020-02-25
• Study Completion: 2020-02-25
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-13
• Last Update Posted: 2024-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Age equal to or greater than 18 years.
• Dialysis vintage equal to or greater than 3 months.

Exclusion Criteria

• Smoking history of more than 10 packs/year.
• Active tobacco and/or cannabis smoking.
• Diagnosed chronic pulmonary disease.
• Severe heart failure (NYHA class IV)
• Active infection (including tuberculosis) or malignancy.
• Pregnancy.
• Inability to give consent or understand written information.
• Peripheral oxygen saturation (by pulse oxymetry) dropping below 80% when performing a 12-seconds breathhold.
• Inability to perform spirometry or plethysmography maneuvers.
• Inability to tolerate MRI due to patient size and/or known history of claustrophobia.
• Subject has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants.).

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Maintenance Hemodialysis Patients	Lung MRI	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires
Maintenance Hemodialysis Patients	Sodium MRI	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires
Maintenance Hemodialysis Patients	Chest CT	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires
Maintenance Hemodialysis Patients	Echocardiography	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires
Maintenance Hemodialysis Patients	Six-Minute Walk Test	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires
Maintenance Hemodialysis Patients	Fractional Exhaled Nitric Oxide	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires
Maintenance Hemodialysis Patients	Pulmonary Function Tests	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires
Maintenance Hemodialysis Patients	Blood Sampling	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires
Maintenance Hemodialysis Patients	Dyspnea Questionnaires	Patients on chronic hemodialysis therapy due to end-stage renal disease. * Proton Lung MRI * Sodium MRI of the leg * Chest CT * Transthoracic Echocardiography * Fractional Exhaled Nitric Oxide * Six-Minute Walk Test * Pulmonary Function Tests * Blood sampling * Self-administered dyspnea questionnaires

Primary Outcome Measures

Name	Time	Method
Baseline Modified Medical Research Council scale score.	Baseline	Baseline dyspnea measured by Modified Medical Research Council scale. 0-4 from lowest (no dyspnea) to highest (most severe dyspnea).
Baseline University of California, San Diego Shortness of Breath Questionnaire score.	Baseline	Baseline dyspnea measured by University of California, San Diego Shortness of Breath Questionnaire.; 0-120 from lowest (no dyspnea) to highest (most severe dyspnea).
Baseline pulmonary artery diameter.	Baseline	Baseline pulmonary artery diameter (in millimeters) by chest Computed Tomography.
Baseline lung low attenuation area.	Baseline	Baseline lung low attenuation area by chest Computed Tomography.
Baseline lung water content.	Baseline	Baseline lung water content in arbitrary units measured by proton Magnetic Resonance Imaging.
Baseline lung total blood vessel volume.	Baseline	Baseline lung total blood vessel volume in ml by chest Computed Tomography.
Baseline lung total airway count.	Baseline	Baseline lung total airway count by chest Computed Tomography.
Baseline soft tissue sodium content.	Baseline	Baseline soft tissue sodium content in mmol/L measured by sodium Magnetic Resonance Imaging.

Secondary Outcome Measures

Name	Time	Method
One year changes in Modified Medical Research Council scale score.	Baseline and one year	Comparison of dyspnea measured by Modified Medical Research Council scale at one year versus baseline.; 0-4 from lowest (no dyspnea) to highest (most severe dyspnea).
Correlation between baseline modified Medical Research Council scale score and one year mortality.	Baseline and one year	One year mortality risk by modified Medical Research Council scale baseline score.
Correlation between modified Medical Research Council scale score and soft tissue sodium content.	Baseline and one year	Correlation coefficient between soft tissue sodium content (mmol/L) and modified Medical Research Council scale score.
Correlation between baseline modified Medical Research Council scale score and one year morbidity.	Baseline and one year	One year morbidity risk by modified Medical Research Council scale baseline score.
Correlation between modified Medical Research Council scale score and lung total airway count.	Baseline and one year	Correlation coefficient between modified Medical Research Council scale score and lung total airway count, measured by chest Computed Tomography.
Correlation between modified Medical Research Council scale score and lung low attenuation areas.	Baseline and one year	Correlation coefficient between modified Medical Research Council scale score and lung low attenuation areas, measured by chest Computed Tomography.
Correlation between modified Medical Research Council scale score and pulmonary artery diameter.	Baseline and one year	Correlation coefficient between modified Medical Research Council scale score and pulmonary artery diameter (in millimeters), measured by chest Computed Tomography.
Correlation between modified Medical Research Council scale score and lung total water content.	Baseline and one year	Correlation coefficient between modified Medical Research Council scale score and lung total water content (in arbitrary units), measured by proton Magnetic Resonance Imaging.
Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year morbidity.	Baseline and one year	One year morbidity risk by University of California, San Diego Shortness of Breath Questionnaire baseline score.
Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year mortality.	Baseline and one year	One year mortality risk by University of California, San Diego Shortness of Breath Questionnaire baseline score.
Correlation between modified Medical Research Council scale score and lung total blood vessel volume.	Baseline and one year	Correlation coefficient between modified Medical Research Council scale score and lung total blood vessel volume (in milliliters), measured by chest Computed Tomography.
One year changes in University of California, San Diego Shortness of Breath Questionnaire score.	Baseline and one year	Comparison of dyspnea measured by University of California, San Diego Shortness of Breath Questionnaire at one year versus baseline.; 0-120 from lowest (no dyspnea) to highest (most severe dyspnea).
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and soft tissue sodium content.	Baseline and one year	Correlation coefficient between soft tissue sodium content (mmol/L) and University of California, San Diego Shortness of Breath Questionnaire score.
Baseline fractional exhaled nitric oxide.	Baseline	Baseline fractional exhaled nitric oxide measured (in parts per billion).
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and pulmonary artery diameter.	Baseline and one year	Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and pulmonary artery diameter (in millimeters), measured by chest Computed Tomography.
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total airway count.	Baseline and one year	Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung total airway count, measured by chest Computed Tomography.
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung low attenuation areas.	Baseline and one year	Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung low attenuation areas, measured by chest Computed Tomography.
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total blood vessel volume.	Baseline and one year	Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung total blood vessel volume (in milliliters), measured by chest Computed Tomography.
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total water content.	Baseline and one year	Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung total water content (in arbitrary units), measured by proton Magnetic Resonance Imaging.
One year changes in lung total blood vessel volume.	Baseline and one year	Comparison of lung total blood vessel volume (in milliliters) at one year versus baseline, measured by chest Computed Tomography.
One year changes in lung low attenuation areas.	Baseline and one year	Comparison of lung low attenuation areas at one year versus baseline, measured by chest Computed Tomography.
One year changes in fractional exhaled nitric oxide.	Baseline and one year	Comparison of fractional exhaled nitric oxide measured (in parts per billion) at one year versus baseline.
One year changes in lung total airway count.	Baseline and one year	Comparison of lung total airway count at one year versus baseline, measured by chest Computed Tomography.
One year changes in lung water content.	Baseline and one year	Comparison of lung water content (in arbitrary units) at one year versus baseline, measured by proton Magnetic Resonance Imaging.
Baseline pulmonary artery systolic pressure.	Baseline	Baseline pulmonary artery systolic pressure (in mmHg), measured by transthoracic doppler echocardiography.
One year changes in pulmonary artery systolic pressure.	Baseline and one year	Comparison of pulmonary artery systolic pressure in mmHg at one year versus baseline, measured by transthoracic doppler echocardiography.
Baseline forced expiratory volume at one second/forced vital capacity ratio.	Baseline	Baseline forced expiratory volume at one second/forced vital capacity ratio by pulmonary function tests.
One year changes in pulmonary artery diameter.	Baseline and one year	Comparison of pulmonary artery diameter (in millimeters) at one year versus baseline, measured by chest Computed Tomography.
One year changes in forced expiratory volume at one second/forced vital capacity ratio.	Baseline and one year	Comparison of forced expiratory volume at one second/forced vital capacity ratio at one year versus baseline, by pulmonary function tests.
Baseline diffusing capacity of the lung for carbon monoxide.	Baseline	Baseline diffusing capacity of the lung for carbon monoxide (in ml/min/kPa), by pulmonary function tests.
One year changes in diffusing capacity of the lung for carbon monoxide.	Baseline and one year	Comparison of diffusing capacity of the lung for carbon monoxide (in ml/min/kPa) at one year versus baseline, by pulmonary function tests
Baseline six minute walk distance.	Baseline	Baseline six minute walk distance (in meters) measured by six minute walk test.
One year changes in six minute walk distance.	Baseline and one year	Comparison of six minute walk distance (in meters) at one year versus baseline, measured by six minute walk test.
One year changes in soft tissue sodium content.	Baseline and one year	Comparison of soft tissue sodium content (in mmol/L) at one year versus baseline, measured by sodium Magnetic Resonance Imaging.

Trial Locations

Locations (1)

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada