Coronary Microvascular Dysfunction in Chronic Kidney Disease

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

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.

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.

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