Coronary Microvascular Dysfunction in Chronic Kidney Disease (CRIB-FLOW)

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.

Study Overview

• Status: Unknown
• 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

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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Ashwin Radhakrishnan, BM MRCP; Phone Number: +447756931470; Email: a.radhakrishnan@nhs.net

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Recruiting
    • Queen Elizabeth Hospital
    • Contact: Ashwin Radhakrishnan, BM MRCP; Phone Number: +447756931470; Email: a.radhakrishnan@nhs.net
    • Principal Investigator: Jonathan N Townend, MD FRCP FESC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients attending University Hospitals Birmingham.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls; 25 controls with preserved renal function	Diagnostic test: Coronary flow reserve assessment; Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.; Diagnostic test: Sphygmocor; Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device; Diagnostic test: Electrocardiogram; An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease; Other: Blood test; Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury; Other: Urinary albumin/creatinine ratio; Urine will be analysed for albumin/creatinine ratio
Kidney Donors; 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; Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.; Diagnostic test: Sphygmocor; Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device; Diagnostic test: Electrocardiogram; An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease; Other: Blood test; Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury; Other: Urinary albumin/creatinine ratio; Urine will be analysed for albumin/creatinine ratio
Pre-dialysis; 25 patients with pre-dialysis chronic kidney disease stage 5	Diagnostic test: Coronary flow reserve assessment; Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.; Diagnostic test: Sphygmocor; Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device; Diagnostic test: Electrocardiogram; An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease; Other: Blood test; Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury; Other: Urinary albumin/creatinine ratio; Urine will be analysed for albumin/creatinine ratio
Peritoneal dialysis; 25 patients with chronic kidney disease stage 5 undergoing peritoneal dialysis	Diagnostic test: Coronary flow reserve assessment; Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.; Diagnostic test: Sphygmocor; Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device; Diagnostic test: Electrocardiogram; An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease; Other: Blood test; Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury; Other: Urinary albumin/creatinine ratio; Urine will be analysed for albumin/creatinine ratio

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulse wave analysis	Augmentation index measured using the Sphygmocor device. Data will be presented as %.	One baseline visit
Pulse wave velocity	Pulse wave velocity measured using the Sphygmocor device. Data will be presented as m/s	One baseline visit

Collaborators and Investigators

• Sponsor: University Hospital Birmingham NHS Foundation Trust
• Investigators: Principal Investigator: Jonathan N Townend, MD FRCP FESC, University Hospitals Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2019
• Primary Completion (Anticipated): August 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: peritoneal dialysis; coronary flow reserve; living kidney donation
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: RRK6607

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No