Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01769924 |
| Other study ID # |
A092761 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 2013 |
| Est. completion date |
March 2017 |
Study information
| Verified date |
February 2022 |
| Source |
Cambridge University Hospitals NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Studies of patients with established kidney disease, even when this is mild, appear to show
that they are at high risk of heart failure, stroke and sudden cardiac death. This may be
because kidney disease causes stiffening of the arteries in the body which means that the
heart and brain are damaged by high blood pressure. By studying patients before and after the
removal of a kidney (uni-nephrectomy) for transplantation the investigators will find out for
the first time in man the effect of an isolated reduction in kidney function on the structure
and function of the cardiovascular system.
Description:
HYPOTHESIS
In living kidney donors, reduction in GFR post-nephrectomy results in:
1. A pressure-independent increase in aortic stiffness (aPWV)
2. An increase in peripheral and central blood pressure
EXPERIMENTAL DETAILS AND DESIGN OF PROPOSED INVESTIGATION We propose a prospective,
longitudinal parallel group study of 200 kidney donors and 200 controls to be recruited over
two years and followed up over one year.
Subjects: The only inclusion criterion is that subjects will be scheduled for nephrectomy for
the purpose of kidney donation. Subjects will be recruited from centres, chosen because of
their high numbers of live donor transplants and strength in vascular research.
Controls: We will recruit a carefully matched series of control patients from the same living
donor clinics at which subjects are identified, who after screening are found to be fit for
donation but do not proceed to surgery.
Exclusion criteria for both subjects and controls: These will be the current nationally set
exclusion criteria for donors and will include diabetes mellitus, any history of
cardiovascular or pulmonary disease, evidence of hypertensive end-organ damage, LV
dysfunction (EF < 40%) and atrial fibrillation.49
Primary endpoint: Change in aPWV at 12 months adjusted for mean arterial pressure and heart
rate at time of measurement compared with controls.
Secondary endpoints: Change in ambulatory blood pressure, AIx, central aortic pressure and
urinary ACR compared with controls.
Secondary analysis: Change in endpoints will be analysed according to baseline GFR, change in
GFR, pre-donation hypertension and ethnic group.
Investigations:
The following investigations will be performed in all subjects and controls at baseline (<6
weeks pre-donation) and 1 year post-donation. Subjects and controls will undergo routine
follow up by the renal team with no alteration to normal care. No restrictions will be made
to the introduction of any treatment including anti-hypertensive drugs. At baseline BMI,
blood pressure and heart rate will be recorded. Routine haematological and biochemical
parameters including lipids will be recorded. The following additional parameters will be
determined:
1. Arterial stiffness: A Sphygmocor device will be used to measure parameters including
aPWV, AIx and central aortic pressure.
2. Spot urine samples will be collected for measurement of ACR.
3. Clinic blood pressure
4. 24-hour ambulatory blood pressure studies (24h ABPM)
5. Isotope GFR for kidney donors will be measured using the renal clearance of 51Cr EDTA50,
in keeping with national recommendations. Kidney function in controls will be estimated
using MDRD eGFR to minimise radiation exposure and cost.
STATISTICS The original recruitment target was 800 patients. Power calculations used a SD of
1.0 m/s in aPWV and 10 mm Hg in blood pressure and a sample size of 800 patients (control and
donors, 400 subjects each). This gives 80% power to detect a difference of 0.22 m/s or 2.2 mm
Hg for aPWV and blood pressure allowing for 9% drop out. This is a 2-sided t test at the 2.5%
significance level. During the study it was apparent the original recruitment target would
not be met therefore a new sample size was calculated.
New power calculations:
Using a SD of 1.0m/s in aPWV and a sample size of 400 patients (control and donors, 200
subjects each). This gives a 92% power to detect a difference of 0.4m/s for aPWV and 4mm Hg
for blood pressure allowing for 15% drop out (alpha at 5%). This is a 2-sided t test at the
2.5% significance level. Following this we aimed for a sample size of 400 patients (200
controls and 200 donors) for determination of the primary outcome of PWV in both groups.
