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.
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 Type
OBSERVATIONAL
Enrollment
7
Proton Lung Magnetic Resonance Imaging
Sodium Soft Tissue Magnetic Resonance Imaging
High-resolution Quantitative Chest CT
Transthoracic 2D Speckle-Tracking Echocardiography
Fractional Exhaled Nitric Oxide testing
Spirometry and Plethysmography
Blood testing for: standard-of-care, inflammatory biomarkers, uremic toxins
Six-Minute Walk Test
Modified Medical Research Council; University of California, San Diego Shortness of Breath Questionnaire; Borg Scale
London Health Sciences Centre
London, Ontario, Canada
Baseline Modified Medical Research Council scale score.
Baseline dyspnea measured by Modified Medical Research Council scale. 0-4 from lowest (no dyspnea) to highest (most severe dyspnea).
Time frame: Baseline
Baseline University of California, San Diego Shortness of Breath Questionnaire score.
Baseline dyspnea measured by University of California, San Diego Shortness of Breath Questionnaire. 0-120 from lowest (no dyspnea) to highest (most severe dyspnea).
Time frame: Baseline
Baseline pulmonary artery diameter.
Baseline pulmonary artery diameter (in millimeters) by chest Computed Tomography.
Time frame: Baseline
Baseline lung total blood vessel volume.
Baseline lung total blood vessel volume in ml by chest Computed Tomography.
Time frame: Baseline
Baseline lung total airway count.
Baseline lung total airway count by chest Computed Tomography.
Time frame: Baseline
Baseline lung low attenuation area.
Baseline lung low attenuation area by chest Computed Tomography.
Time frame: Baseline
Baseline lung water content.
Baseline lung water content in arbitrary units measured by proton Magnetic Resonance Imaging.
Time frame: Baseline
Baseline soft tissue sodium content.
Baseline soft tissue sodium content in mmol/L measured by sodium Magnetic Resonance Imaging.
Time frame: Baseline
One year changes in Modified Medical Research Council scale score.
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).
Time frame: Baseline and one year
Correlation between baseline modified Medical Research Council scale score and one year morbidity.
One year morbidity risk by modified Medical Research Council scale baseline score.
Time frame: Baseline and one year
Correlation between baseline modified Medical Research Council scale score and one year mortality.
One year mortality risk by modified Medical Research Council scale baseline score.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and soft tissue sodium content.
Correlation coefficient between soft tissue sodium content (mmol/L) and modified Medical Research Council scale score.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and pulmonary artery diameter.
Correlation coefficient between modified Medical Research Council scale score and pulmonary artery diameter (in millimeters), measured by chest Computed Tomography.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total blood vessel volume.
Correlation coefficient between modified Medical Research Council scale score and lung total blood vessel volume (in milliliters), measured by chest Computed Tomography.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total airway count.
Correlation coefficient between modified Medical Research Council scale score and lung total airway count, measured by chest Computed Tomography.
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Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and lung low attenuation areas.
Correlation coefficient between modified Medical Research Council scale score and lung low attenuation areas, measured by chest Computed Tomography.
Time frame: Baseline and one year
Correlation between modified Medical Research Council scale score and lung total water content.
Correlation coefficient between modified Medical Research Council scale score and lung total water content (in arbitrary units), measured by proton Magnetic Resonance Imaging.
Time frame: Baseline and one year
One year changes in University of California, San Diego Shortness of Breath Questionnaire score.
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).
Time frame: Baseline and one year
Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year morbidity.
One year morbidity risk by University of California, San Diego Shortness of Breath Questionnaire baseline score.
Time frame: Baseline and one year
Correlation between baseline University of California, San Diego Shortness of Breath Questionnaire score and one year mortality.
One year mortality risk by University of California, San Diego Shortness of Breath Questionnaire baseline score.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and pulmonary artery diameter.
Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and pulmonary artery diameter (in millimeters), measured by chest Computed Tomography.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and soft tissue sodium content.
Correlation coefficient between soft tissue sodium content (mmol/L) and University of California, San Diego Shortness of Breath Questionnaire score.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total blood vessel volume.
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.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total airway count.
Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung total airway count, measured by chest Computed Tomography.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung low attenuation areas.
Correlation coefficient between University of California, San Diego Shortness of Breath Questionnaire score and lung low attenuation areas, measured by chest Computed Tomography.
Time frame: Baseline and one year
Correlation between University of California, San Diego Shortness of Breath Questionnaire score and lung total water content.
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.
Time frame: Baseline and one year
One year changes in lung total blood vessel volume.
Comparison of lung total blood vessel volume (in milliliters) at one year versus baseline, measured by chest Computed Tomography.
Time frame: Baseline and one year
One year changes in lung total airway count.
Comparison of lung total airway count at one year versus baseline, measured by chest Computed Tomography.
Time frame: Baseline and one year
One year changes in lung water content.
Comparison of lung water content (in arbitrary units) at one year versus baseline, measured by proton Magnetic Resonance Imaging.
Time frame: Baseline and one year
One year changes in lung low attenuation areas.
Comparison of lung low attenuation areas at one year versus baseline, measured by chest Computed Tomography.
Time frame: Baseline and one year
One year changes in pulmonary artery diameter.
Comparison of pulmonary artery diameter (in millimeters) at one year versus baseline, measured by chest Computed Tomography.
Time frame: Baseline and one year
Baseline pulmonary artery systolic pressure.
Baseline pulmonary artery systolic pressure (in mmHg), measured by transthoracic doppler echocardiography.
Time frame: Baseline
One year changes in pulmonary artery systolic pressure.
Comparison of pulmonary artery systolic pressure in mmHg at one year versus baseline, measured by transthoracic doppler echocardiography.
Time frame: Baseline and one year
Baseline fractional exhaled nitric oxide.
Baseline fractional exhaled nitric oxide measured (in parts per billion).
Time frame: Baseline
One year changes in fractional exhaled nitric oxide.
Comparison of fractional exhaled nitric oxide measured (in parts per billion) at one year versus baseline.
Time frame: Baseline and one year
Baseline forced expiratory volume at one second/forced vital capacity ratio.
Baseline forced expiratory volume at one second/forced vital capacity ratio by pulmonary function tests.
Time frame: Baseline
One year changes in forced expiratory volume at one second/forced vital capacity ratio.
Comparison of forced expiratory volume at one second/forced vital capacity ratio at one year versus baseline, by pulmonary function tests.
Time frame: Baseline and one year
Baseline diffusing capacity of the lung for carbon monoxide.
Baseline diffusing capacity of the lung for carbon monoxide (in ml/min/kPa), by pulmonary function tests.
Time frame: Baseline
One year changes in diffusing capacity of the lung for carbon monoxide.
Comparison of diffusing capacity of the lung for carbon monoxide (in ml/min/kPa) at one year versus baseline, by pulmonary function tests
Time frame: Baseline and one year
Baseline six minute walk distance.
Baseline six minute walk distance (in meters) measured by six minute walk test.
Time frame: Baseline
One year changes in six minute walk distance.
Comparison of six minute walk distance (in meters) at one year versus baseline, measured by six minute walk test.
Time frame: Baseline and one year
One year changes in soft tissue sodium content.
Comparison of soft tissue sodium content (in mmol/L) at one year versus baseline, measured by sodium Magnetic Resonance Imaging.
Time frame: Baseline and one year