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.

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.).

The patients for this trial will be recruited from incident and prevalent hemodialysis patients receiving care for their kidney disease from the Dialysis Service at London Health Sciences Centre, London Ontario. Up to 20 eligible patients will be recruited.