Dyspnea Assessment in Hemodialysis Patients

End Stage Renal Disease Clinical Trial

Official title:

Multimodal Assessment of Dyspnea, Cardiopulmonary Structure and Function in Chronic Hemodialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03773991
• Other study ID #: 110256
• Status: Completed
• Start date: March 29, 2019
• Est. completion date: February 25, 2020

Study information

• Verified date: April 2024
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: February 25, 2020
• Est. primary completion date: February 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.).

Related Conditions & MeSH terms

• Chronic Heart Disease
• Chronic Lung Disease
• Dyspnea
• Dyspnea; Uremic
• End Stage Renal Disease
• Heart Diseases
• Hemodialysis-Induced Symptom
• Kidney Diseases
• Kidney Failure, Chronic
• Lung Diseases
• Sodium Excess

Intervention

Diagnostic Test:
• Lung MRI
Proton Lung Magnetic Resonance Imaging
• Sodium MRI
Sodium Soft Tissue Magnetic Resonance Imaging
• Chest CT
High-resolution Quantitative Chest CT
• Echocardiography
Transthoracic 2D Speckle-Tracking Echocardiography
• Fractional Exhaled Nitric Oxide
Fractional Exhaled Nitric Oxide testing
• Pulmonary Function Tests
Spirometry and Plethysmography
• Blood Sampling
Blood testing for: standard-of-care, inflammatory biomarkers, uremic toxins
• Six-Minute Walk Test
Six-Minute Walk Test
• Dyspnea Questionnaires
Modified Medical Research Council; University of California, San Diego Shortness of Breath Questionnaire; Borg Scale

Locations

Country	Name	City	State
Canada	London Health Sciences Centre	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	Western University, Canada

Country where clinical trial is conducted

Canada, 

References & Publications (15)

Barak M, Nakhoul F, Katz Y. Pathophysiology and clinical implications of microbubbles during hemodialysis. Semin Dial. 2008 May-Jun;21(3):232-8. doi: 10.1111/j.1525-139X.2008.00424.x. Epub 2008 Mar 18. — View Citation

Belem LC, Zanetti G, Souza AS Jr, Hochhegger B, Guimaraes MD, Nobre LF, Rodrigues RS, Marchiori E. Metastatic pulmonary calcification: state-of-the-art review focused on imaging findings. Respir Med. 2014 May;108(5):668-76. doi: 10.1016/j.rmed.2014.01.012. Epub 2014 Feb 6. — View Citation

Bolignano D, Rastelli S, Agarwal R, Fliser D, Massy Z, Ortiz A, Wiecek A, Martinez-Castelao A, Covic A, Goldsmith D, Suleymanlar G, Lindholm B, Parati G, Sicari R, Gargani L, Mallamaci F, London G, Zoccali C. Pulmonary hypertension in CKD. Am J Kidney Dis. 2013 Apr;61(4):612-22. doi: 10.1053/j.ajkd.2012.07.029. Epub 2012 Nov 17. Erratum In: Am J Kidney Dis. 2015 Mar;65(3):524. — View Citation

Fairshter RD, Vaziri ND, Mirahmadi MK. Lung pathology in chronic hemodialysis patients. Int J Artif Organs. 1982 Mar;5(2):97-100. — View Citation

Herrero JA, Alvarez-Sala JL, Coronel F, Moratilla C, Gamez C, Sanchez-Alarcos JM, Barrientos A. Pulmonary diffusing capacity in chronic dialysis patients. Respir Med. 2002 Jul;96(7):487-92. doi: 10.1053/rmed.2002.1346. — View Citation

Incalzi RA, Corsonello A, Pedone C, Battaglia S, Paglino G, Bellia V; Extrapulmonary Consequences of COPD in the Elderly Study Investigators. Chronic renal failure: a neglected comorbidity of COPD. Chest. 2010 Apr;137(4):831-7. doi: 10.1378/chest.09-1710. Epub 2009 Nov 10. — View Citation

Kovacevic P, Stanetic M, Rajkovaca Z, Meyer FJ, Vukoja M. Changes in spirometry over time in uremic patients receiving long-term hemodialysis therapy. Pneumologia. 2011 Jan-Mar;60(1):36-9. — View Citation

McIntyre CW, Odudu A. Hemodialysis-associated cardiomyopathy: a newly defined disease entity. Semin Dial. 2014 Mar;27(2):87-97. doi: 10.1111/sdi.12197. — View Citation

Murtagh FE, Addington-Hall JM, Edmonds PM, Donohoe P, Carey I, Jenkins K, Higginson IJ. Symptoms in advanced renal disease: a cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis. J Palliat Med. 2007 Dec;10(6):1266-76. doi: 10.1089/jpm.2007.0017. — View Citation

Nascimento MM, Qureshi AR, Stenvinkel P, Pecoits-Filho R, Heimburger O, Cederholm T, Lindholm B, Barany P. Malnutrition and inflammation are associated with impaired pulmonary function in patients with chronic kidney disease. Nephrol Dial Transplant. 2004 Jul;19(7):1823-8. doi: 10.1093/ndt/gfh190. Epub 2004 May 18. — View Citation

Pabst S, Hammerstingl C, Hundt F, Gerhardt T, Grohe C, Nickenig G, Woitas R, Skowasch D. Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study. PLoS One. 2012;7(4):e35310. doi: 10.1371/journal.pone.0035310. Epub 2012 Apr 18. — View Citation

Plesner LL, Warming PE, Nielsen TL, Dalsgaard M, Schou M, Host U, Rydahl C, Brandi L, Kober L, Vestbo J, Iversen K. Chronic obstructive pulmonary disease in patients with end-stage kidney disease on hemodialysis. Hemodial Int. 2016 Jan;20(1):68-77. doi: 10.1111/hdi.12342. Epub 2015 Aug 5. — View Citation

Romoff MS, Keusch G, Campese VM, Wang MS, Friedler RM, Weidmann P, Massry SG. Effect of sodium intake on plasma catecholamines in normal subjects. J Clin Endocrinol Metab. 1979 Jan;48(1):26-31. doi: 10.1210/jcem-48-1-26. No abstract available. — View Citation

Wallin CJ, Jacobson SH, Leksell LG. Subclinical pulmonary oedema and intermittent haemodialysis. Nephrol Dial Transplant. 1996 Nov;11(11):2269-75. doi: 10.1093/oxfordjournals.ndt.a027147. — View Citation

Zoccali C, Torino C, Tripepi R, Tripepi G, D'Arrigo G, Postorino M, Gargani L, Sicari R, Picano E, Mallamaci F; Lung US in CKD Working Group. Pulmonary congestion predicts cardiac events and mortality in ESRD. J Am Soc Nephrol. 2013 Mar;24(4):639-46. doi: 10.1681/ASN.2012100990. Epub 2013 Feb 28. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Baseline
Primary	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).	Baseline
Primary	Baseline pulmonary artery diameter.	Baseline pulmonary artery diameter (in millimeters) by chest Computed Tomography.	Baseline
Primary	Baseline lung total blood vessel volume.	Baseline lung total blood vessel volume in ml by chest Computed Tomography.	Baseline
Primary	Baseline lung total airway count.	Baseline lung total airway count by chest Computed Tomography.	Baseline
Primary	Baseline lung low attenuation area.	Baseline lung low attenuation area by chest Computed Tomography.	Baseline
Primary	Baseline lung water content.	Baseline lung water content in arbitrary units measured by proton Magnetic Resonance Imaging.	Baseline
Primary	Baseline soft tissue sodium content.	Baseline soft tissue sodium content in mmol/L measured by sodium Magnetic Resonance Imaging.	Baseline
Secondary	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).	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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).	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	One year changes in lung total airway count.	Comparison of lung total airway count at one year versus baseline, measured by chest Computed Tomography.	Baseline and one year
Secondary	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.	Baseline and one year
Secondary	One year changes in lung low attenuation areas.	Comparison of lung low attenuation areas at one year versus baseline, measured by chest Computed Tomography.	Baseline and one year
Secondary	One year changes in pulmonary artery diameter.	Comparison of pulmonary artery diameter (in millimeters) at one year versus baseline, measured by chest Computed Tomography.	Baseline and one year
Secondary	Baseline pulmonary artery systolic pressure.	Baseline pulmonary artery systolic pressure (in mmHg), measured by transthoracic doppler echocardiography.	Baseline
Secondary	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.	Baseline and one year
Secondary	Baseline fractional exhaled nitric oxide.	Baseline fractional exhaled nitric oxide measured (in parts per billion).	Baseline
Secondary	One year changes in fractional exhaled nitric oxide.	Comparison of fractional exhaled nitric oxide measured (in parts per billion) at one year versus baseline.	Baseline and one year
Secondary	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.	Baseline
Secondary	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.	Baseline and one year
Secondary	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.	Baseline
Secondary	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	Baseline and one year
Secondary	Baseline six minute walk distance.	Baseline six minute walk distance (in meters) measured by six minute walk test.	Baseline
Secondary	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.	Baseline and one year
Secondary	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.	Baseline and one year