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Effects of a Reduction in Renal Function on Cardiovascular Structure and Function (CRIB-DONOR II)

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ClinicalTrials.gov Identifier: NCT02973607
Recruitment Status : Recruiting
First Posted : November 25, 2016
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Anna Price, University Hospital Birmingham NHS Foundation Trust

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.


Condition or disease Intervention/treatment
Chronic Kidney Disease Hypertrophy, Left Ventricular Hypertension Procedure: Nephrectomy

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.


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Study Type : Observational
Estimated Enrollment : 124 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Effects of a Reduction in Renal Function on Cardiovascular Structure and Function: A 5 Year Study of Kidney Donors.
Actual Study Start Date : May 23, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests

Group/Cohort Intervention/treatment
Donors
Patients who donated a kidney and took part in the original CRIB-DONOR study.
Procedure: Nephrectomy
This is observational in design.

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



Primary Outcome Measures :
  1. Left ventricular mass and interstitial fibrosis [ Time Frame: 3 years ]
    Measured by CMR (part 1 of study).


Secondary Outcome Measures :
  1. Aortic compliance [ Time Frame: 3 years ]
    Measured by CMR (part 1 of study).

  2. Cardiovascular age [ Time Frame: 3 years ]
    Measured by telomere length and studies of DNA damage (part 1 and 2 of study).

  3. Oxidative stress, inflammation and collagen turnover [ Time Frame: 3 years ]
    Measured by assay and bioassay (part 1 of study).

  4. Blood pressure [ Time Frame: 3 years ]
    Measured by ambulatory blood pressure monitoring (part 1 of study).


Biospecimen Retention:   Samples With DNA
Serum, plasma, acellular urine and DNA (for telomere length).


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Living donors and healthy controls
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02973607


Contacts
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Contact: Dr Anna Price, MbChB 0121 371 4624 anna.price@uhb.nhs.uk

Locations
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United Kingdom
Queen Elizabeth Hospital Birmingham Recruiting
Birmingham, West Midlands, United Kingdom, B15 2TH
Contact: Anna Price         
Sponsors and Collaborators
University Hospital Birmingham NHS Foundation Trust
Investigators
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Principal Investigator: Professor John Townend, MbChB University Hospital Birmingham NHS Foundation Trust

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Responsible Party: Anna Price, Principal Investigator, University Hospital Birmingham NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02973607     History of Changes
Other Study ID Numbers: RRK5913
First Posted: November 25, 2016    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Hypertrophy, Left Ventricular
Hypertrophy
Cardiovascular Diseases
Urologic Diseases
Renal Insufficiency
Pathological Conditions, Anatomical
Cardiomegaly
Heart Diseases