Coronary Microvascular Dysfunction in Chronic Kidney Disease

Study Overview
=================
Brief Summary
-----------------
This is an observational study assessing coronary microvascular function in healthy controls with normal kidney function, living kidney donors, pre-dialysis patients with chronic kidney disease stage 5 and patients on peritoneal dialysis.

Detailed Description
-----------------
The clinical syndrome of uraemic cardiomyopathy is prevalent in end stage renal disease and is associated with pathological cardiovascular changes including left ventricular hypertrophy, diastolic dysfunction and diffuse interstitial fibrosis. These combine to confer an elevated cardiovascular risk, including an increased risk of sudden cardiac death. The cause of this increased cardiovascular risk is not clear but it is thought that coronary microvascular dysfunction may play a role. Coronary microvascular dysfunction is prevalent in many myocardial disease states, such as hypertrophic cardiomyopathy and heart failure with preserved ejection fraction, that share pathological similarities with uraemic cardiomyopathy. Coronary flow reserve, a marker of coronary microvascular function, can be assessed non-invasively using echocardiography techniques. Previous studies have shown a reduction in coronary flow reserve in patients with chronic kidney disease. However, it is not clear if kidney donors - individuals who have a reduced kidney function but do not have progressive kidney disease - also demonstrate microvascular dysfunction. Similarly, although there is some evidence that patients on dialysis have improved coronary flow reserve compared to patients with pre-dialysis chronic kidney disease stage 5, there has been limited investigation into the role of peritoneal dialysis on coronary flow reserve.

Official Title
-----------------
Coronary Microvascular Dysfunction in Chronic Kidney Disease: The Chronic Renal Impairment in Birmingham Coronary Flow Reserve (CRIB FLOW) Study

Conditions
-----------------
Kidney Disease, Chronic, Myocardial Dysfunction

Intervention / Treatment
-----------------
* Diagnostic Test: Coronary flow reserve assessment
* Diagnostic Test: Sphygmocor
* Diagnostic Test: Electrocardiogram
* Other: Blood test
* Other: Urinary albumin/creatinine ratio


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy control with normal renal function Living kidney donor who has donated >12 months prior to enrolment in study Chronic kidney disease stage 5 who are pre-dialysis or on peritoneal dialysis Able to provide written informed consent Exclusion Criteria: Pregnancy Known ischaemic heart disease Diabetes mellitus Uncontrolled hypertension Evidence of 2nd or 3rd degree AV block or sick sinus syndrome in absence of a pacemaker History of allergic/adverse reaction to adenosine or Sonovue History of long QT syndrome Severe hypotension Significant valvular heart disease Significant chronic obstructive pulmonary disease or asthma with bronchospasm Unstable angina not controlled with medication Concurrent use of dipyridamole Decompensated heart failure Poor echo acoustic windows Chronic kidney disease stage 5 on haemodialysis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Controls<br>25 controls with preserved renal function | Diagnostic Test: Coronary flow reserve assessment<br>* Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.<br>Diagnostic Test: Sphygmocor<br>* Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device<br>Diagnostic Test: Electrocardiogram<br>* An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease<br>Other: Blood test<br>* Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury<br>Other: Urinary albumin/creatinine ratio<br>* Urine will be analysed for albumin/creatinine ratio<br>|
| Kidney Donors<br>25 living kidney donors who have donated a kidney at least 12 months prior to enrollment in the study. | Diagnostic Test: Coronary flow reserve assessment<br>* Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.<br>Diagnostic Test: Sphygmocor<br>* Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device<br>Diagnostic Test: Electrocardiogram<br>* An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease<br>Other: Blood test<br>* Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury<br>Other: Urinary albumin/creatinine ratio<br>* Urine will be analysed for albumin/creatinine ratio<br>|
| Pre-dialysis<br>25 patients with pre-dialysis chronic kidney disease stage 5 | Diagnostic Test: Coronary flow reserve assessment<br>* Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.<br>Diagnostic Test: Sphygmocor<br>* Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device<br>Diagnostic Test: Electrocardiogram<br>* An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease<br>Other: Blood test<br>* Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury<br>Other: Urinary albumin/creatinine ratio<br>* Urine will be analysed for albumin/creatinine ratio<br>|
| Peritoneal dialysis<br>25 patients with chronic kidney disease stage 5 undergoing peritoneal dialysis | Diagnostic Test: Coronary flow reserve assessment<br>* Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.<br>Diagnostic Test: Sphygmocor<br>* Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device<br>Diagnostic Test: Electrocardiogram<br>* An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease<br>Other: Blood test<br>* Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury<br>Other: Urinary albumin/creatinine ratio<br>* Urine will be analysed for albumin/creatinine ratio<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coronary flow reserve | Ultrasound-assessed coronary flow reserve. Data will be presented as a ratio (no unit) between maximal mean hyperemia flow velocity and baseline velocity | One baseline visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial blood flow | Ultrasound measurement of myocardial blood flow using myocardial contrast echocardiography. Data will be presented as dB/sec | One baseline visit | 
| Left ventricular ejection fraction | Echocardiogram assessed left ventricular ejection fraction by Simpson's biplane method. Data will be presented as %. | One baseline visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
coronary flow reserve, living kidney donation, peritoneal dialysis