MRI Assessment of Myocardial Fibrosis Associated With Monocyte Phenotype in End Stage Renal Failure

Summary

Firstly, this study aims to understand how cardiac fibrosis mediated by inflammatory microvascular disease evolves during advanced chronic kidney disease and end stage renal failure and importantly how this changes with commencement on renal replacement therapy (haemodialysis and peritoneal dialysis) using sequential cardiac MRI imaging. This method of imaging is non-invasive, provides significantly more data than echocardiography, is reproducible and accurate, has been validated in numerous studies and does not involve exposure to ionising radiation.

Secondly, this study aims to examine the changes in monocyte subsets and biochemical profile in peripheral blood prior to, during and after commencement on renal replacement therapy.

The investigators hypothesis would be that renal failure causes alteration in monocyte subset phenotype resulting in increased circulating inflammatory monocytes (human CD14high CD16high), initiating pro-inflammatory cytokine expression and thereby accelerating inflammatory cardiovascular disease and development of myocardial fibrosis.

Conditions

• Myocardial Fibrosis
• End Stage Renal Failure on Dialysis
• Chronic Kidney Disease, Stage IV (Severe)
• Chronic Kidney Disease Stage V
• Heart Failure

Interventions

DIAGNOSTIC_TEST

Cardiac MRI 1 - With Gadolinium Contrast

Cines for cardiac function and volumes, T2 myomaps, Resting perfusion and strain analysis, Tagging (strain), T1 myomaps, Late gadolinium enhancement During the MRI scan participants would be required perform a short period of low intensity exercise involving peddling on an adapted cycle for 10-15 minutes to provide additional data on cardiac function under exertion.

DIAGNOSTIC_TEST

Cardiac MRI 2 - With Gadolinium Contrast

Cines for cardiac function and volumes, T2 myomaps, Resting perfusion and strain analysis, Tagging (strain), T1 myomaps, Late gadolinium enhancement During the MRI scan participants would be required perform a short period of low intensity exercise involving peddling on an adapted cycle for 10-15 minutes to provide additional data on cardiac function under exertion.

DIAGNOSTIC_TEST

Cardiac MRI 3 - Without Gadolinium Contrast

Cines for cardiac function and volumes, T2 myomaps, Resting perfusion and strain analysis, Tagging (strain), T1 myomaps. During the MRI scan participants would be required perform a short period of low intensity exercise involving peddling on an adapted cycle for 10-15 minutes to provide additional data on cardiac function under exertion.

DIAGNOSTIC_TEST

Cardiac MRI 3 - With Gadolinium Contrast

Cines for cardiac function and volumes, T2 myomaps, Resting perfusion and strain analysis, Tagging (strain), T1 myomaps, Late gadolinium enhancement During the MRI scan participants would be required perform a short period of low intensity exercise involving peddling on an adapted cycle for 10-15 minutes to provide additional data on cardiac function under exertion.

DIAGNOSTIC_TEST

Peripheral Whole Blood Samples

20ml EDTA whole blood samples - collected sequentially during study - max 8 time points

Sponsors & Collaborators

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• Imperial College Healthcare NHS Trust

  collaborator OTHER

• Imperial College London

  lead OTHER

Principal Investigators

• Neill Duncan, MBBS FRCP · Imperial College Healthcare NHS Trust

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-02-01

Primary Completion

2021-02-01

Completion

2021-02-01

Countries

• United Kingdom

Study Locations