Effects of a Reduction in Renal Function on Cardiovascular Structure and Function

NCT ID: NCT02973607

Last Updated: 2020-10-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 95 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-05-23
• Study Completion Date: 2020-07-31

Brief Summary

Chronic kidney disease (CKD) is present in 1 in 7 of the population and confers a high risk of cardiovascular disease. The pathophysiology of cardiovascular disease in CKD is poorly understood because CKD is always accompanied by confounding factors including the underlying disease process (e.g. diabetes mellitus, systemic vasculitis) and the consequences of CKD including hypertension, anaemia and inflammation.

Nephrectomy in kidney donors causes a 30% reduction in renal function providing an ideal study population to measure prospectively the effects of reduced kidney function on the cardiovascular system.

The CRIB-Donor study (ClinicalTrials.gov Identifier:NCT01028703) demonstrated adverse effects on cardiovascular structure and function at 12 months compared to controls including an increase in left ventricular mass. This proposal will measure the changes in cardiovascular structure and function, cardiovascular age and biochemical changes at 5 years providing information on the long term effects of reduced renal function.

Detailed Description

A reduction in renal function at one year in kidney donors is associated with adverse cardiovascular structural and functional changes. Increases in LV mass and perhaps fibrosis along with increased arterial stiffness are associated with adverse changes in prognostic imaging biomarkers and may in the long term contribute to the development of clinical disease such as heart failure and arrhythmia.

It is important to follow this valuable and well characterised cohort of subjects to investigate the further natural history of these cardiovascular effects and determine whether such changes tend to regress, stabilise or worsen over time.

Hypotheses:

The reduction in GFR occurring after surgical uni-nephrectomy in donors is associated with long term adverse cardiac and vascular effects which include:

1. A sustained increased in left ventricular mass, impaired left ventricular systolic and diastolic function and increased left ventricular interstitial fibrosis.

2. Reduced aortic distensibility.

3. Increased systolic but not diastolic blood pressure.

4. Increases in oxidative stress, inflammation and collagen turnover

5. Cardiovascular ageing as evidenced by adverse effects on telomere length and DNA damage.

Study design:

We aim to follow up all 124 patients who originally took part in the CRIB-DONOR study at 5 years and eventually 10 years post nephrectomy.

Statistics and sample size:

Using the effect sizes and variances from our previous work (change in LV mass 7g, SD of change 10g) we calculate that by studying 50 subjects in each group we will have 93% power to detect a difference in LV mass of 7g with an alpha value of 0.05. Due to the nature of a follow up study some drop out can be expected. A minimum of 34 patients is required in each group in order to achieve an 80% power. This effect is clinically important; a fall in LV mass index of one SD has been shown to be associated with a 38% reduction in cardiovascular mortality.

With respect to telomere shortening, assuming mean and SD of base pair length of 5500 and 530 the study will be able to detect a difference of 0.612 SD, i.e. 324 base pairs. A sample size of 50 patients per group would provide a 85% power to detect a difference.

Conditions

Chronic Kidney Disease; Hypertrophy, Left Ventricular; Hypertension

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Donors

Patients who donated a kidney and took part in the original CRIB-DONOR study.

Nephrectomy

Intervention Type: PROCEDURE

This is observational in design.

Controls

Healthy subjects who took part in the original CRIB-DONOR study.

No interventions assigned to this group

Interventions

Nephrectomy

This is observational in design.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

All patients who took part in the original CRIB-Donor study.

Exclusion Criteria

Pregnant women

Patients will have previously met nationally set criteria for living donation which excludes those with:

Diabetes mellitus Atrial fibrillation Left ventricular dysfunction (ejection fraction <40% on transthoracic echocardiography) History of cardiovascular or pulmonary disease Evidence of hypertensive end-organ damage.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital Birmingham NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Anna Price

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Professor John Townend, MbChB

Role: PRINCIPAL_INVESTIGATOR

University Hospital Birmingham NHS Foundation Trust

Locations

Queen Elizabeth Hospital Birmingham

Birmingham, West Midlands, United Kingdom

Countries

United Kingdom

Other Identifiers

RRK5913

Identifier Type: -

Identifier Source: org_study_id