Clinical trial NCT03176862: Left Ventricular Fibrosis in Chronic Kidney Disease
Official title: Onset and Functional Consequences of Left Ventricular (LV) Fibrosis in Chronic Kidney
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Kidney Diseases
Cardio-Renal Syndrome
Myocardial Fibrosis
Uraemic Cardiomyopathy
Lead sponsor: University Hospital Birmingham NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
First posted: 2017-06-06
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Stable CKD from early to severe late stage (stage 2 to 5). Patients expected to undergo live-donor kidney transplantation. Healthy controls. Hypertensive controls (stable, well controlled hypertension).

Brief summary: This study aims to understand the onset an functional consequences of left ventricular interstitial fibrosis in patients with chronic kidney disease (stage 2 to 5), as well as assess whether transplantation results in a regression of cardiac fibrosis.Thus all patients will undergo: 1) a cardiac magnetic resonance imaging (MRI) scan to assess cardiac function and measure left ventricular interstitial fibrosis; 2) a cardiopulmonary stress echocardiogram to understand the functional consequences of fibrosis and rule out any underlying ischaemic heart disease; 3) a 24 hour holter monitor and electrocardiogram (ECG) to assess whether these patients are at higher risk of arrhythmia.

Detailed description: Aim and objectives:

The primary objective of this study is to test the following hypotheses:

i) Patients with early stage chronic kidney disease (CKD) exhibit diffuse LV fibrosis manifest by prolonged native myocardial T1 times and expansion of the extracellular volume (ECV) measured on MRI with a graded relationship to eGFR (stage of CKD), independent of blood pressure and arterial stiffness.

The secondary research objectives are to test the following hypotheses:

i) Prolonged native myocardial T1 times are associated with impaired diastolic function, altered arterial-ventricular interaction and impaired effort tolerance.

ii) Prolonged T1 times correlate with increases in serum biomarkers of collagen turnover associated with myocardial fibrosis that could be used to risk stratify individuals and enable targeted, personalized clinical care.

iii) Renal transplantation results in a regression of myocardial fibrosis as measured by T1 mapping.

DESIGN:

A cross-sectional analysis of 40 patients in each stage 2-5 CKD will be undertaken. These individuals will only be studied once (at baseline). In addition to this, at least 20 patients will be studied who are about to undergo a kidney transplant. These individuals will be studied at baseline (around the time of surgery), at 6 weeks post-operatively, and then 1 year post-operatively to assess the effect on renal transplantation on myocardial fibrosis.

SUBJECTS:

Patients will be recruited from the clinics run by University Hospitals Birmingham NHS Foundation Trust (UHB) with stages 2, 3, 4 and 5 CKD defined using eGFR calculated with the 4-variable 'Modification of Diet in Renal Disease' (MDRD) equation, with a minimum of two consecutive tests at least 90 days apart. Forty patients will be recruited per group of CKD. All study subjects will undergo a cardiac MRI scan, a cardiopulmonary exercise tests with stress echocardiogram, a 24-hour ECG holter monitor, and blood tests.

CONTROLS:

Forty healthy control subjects and forty hypertensive control subjects will be studied. All patients will undergo the identical research protocol to the CKD subjects, except they will not have a stress echocardiogram or an ECG holter monitor.

Eligibility criteria: Inclusion Criteria:

* \>18 years old
* CKD stage 2, 3, 4 and 5

Exclusion Criteria:

* Pregnancy
* Ischaemic heart disease (angina, ACS)
* Cerebral vascular disease
* Peripheral vascular disease
* Renovascular disease
* Diabetes mellitus
* Valvular heart disease (more than mild)
* Established diagnosis of heart failure
* Cannot have an MRI scan

Primary outcomes:
measure: The effect of eGFR on heart muscle scarring (measured from cardiac MRI using T1 times).
timeFrame: One baseline visit only
Secondary outcomes:
measure: The relationship between prolonged myocardial T1 and diastolic function.
timeFrame: One baseline visit only
measure: The relationship between prolonged myocardial T1 and effort tolerance.
timeFrame: One baseline visit only
measure: The effect of renal transplantation on myocardial fibrosis.
timeFrame: Baseline visit (pre-operation), then follow up at 6 weeks and 1 year.
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
state: West Midlands
Study officials:
affiliation: University Hospital Birmingham NHS Foundation Trust
name: Nicola C Edwards, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hayer MK, Radhakrishnan A, Price AM, Liu B, Baig S, Weston CJ, Biasiolli L, Ferro CJ, Townend JN, Steeds RP, Edwards NC; Birmingham Cardio-Renal Group. Defining Myocardial Abnormalities Across the Stages of Chronic Kidney Disease: A Cardiac Magnetic Resonance Imaging Study. JACC Cardiovasc Imaging. 2020 Nov;13(11):2357-2367. doi: 10.1016/j.jcmg.2020.04.021. Epub 2020 Jul 15.