Objective: To test the efficacy and safety of percutaneous renal sympathetic denervation of the native kidneys in the treatment of uncontrolled hypertension in kidney transplant recipients.
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: Primary endpoint is the change in blood
pressure after 6 months (mean day time systolic blood pressure assessed by
24-hour ambulatory measurement).
Secondary outcome
Secondary outcomes include changes in office blood pressure, changes in
antihypertensive treatment, plasma catecholamines, renin and aldosterone, eGFR
and 24h proteinuria, Moreover, compliance with antihypertensive treatment
compliance will be measured using a questionnaire and by detection of
antihypertensives in a blood sample.
Background summary
Rationale: In patients with a renal allograft, hypertension is a major
etiological factor for cardiovascular morbidity, mortality and allograft
nephropathy. Controlling hypertension in patients with a renal allograft is
therefore crucial. Despite large patients- and doctors efforts, hypertension
control is insufficient in many kidney transplant recipients. The diseased
native kidneys are major contributors to hypertension, through neuro-hormonal
up-regulation that leads to high levels of renin and sympathetic activity.
Recently a catheter-based approach has been developed to disrupt renal
sympathetic nerves. Currently this innovative technique has only been tested to
lower blood pressure in therapy resistant hypertensive patients without
significant renal disease (METC protocol ID 12-540). We hypothesize that
catheter based selective renal denervation of the native kidneys in renal
transplant recipients will improve blood pressure control and diminish the
number of antihypertensive drugs needed. Before embarking on a large trial, we
propose a feasibility study to obtain estimates of effect and to assess the
feasibility of the procedure in this patient group.
Study objective
Objective: To test the efficacy and safety of percutaneous renal sympathetic
denervation of the native kidneys in the treatment of uncontrolled hypertension
in kidney transplant recipients.
Study design
Study design: We propose an intervention study in 20 kidney transplant
recipients. Renal denervation will be added to usual care in all participants.
Patients will be randomized to renal denervation directly after inclusion or
after 6 months. Both groups will be followed for one year.
Intervention
Intervention: All patients will continue to receive usual antihypertensive
treatment according to prevailing guidelines. Percutaneous renal denervation of
the native kidneys will be performed at the time point determined by the
randomization procedure.
Study burden and risks
Renal denervation is achieved by radio-frequency ablation during
catheterisation of the renal arteries. The risks of catheterisation are
bleeding, infection and contrast-agent induced nephropathy. The actual burden
of the ablation procedure is that it causes visceral pain that will be treated
with appropriate analgesics. Furthermore, the study requires extra visits for
blood pressure measurements and extra blood drawing. The benefit could be
improvement of blood pressure control. There is a sound theoretical background
for application of the renal denervation procedure in kidney transplant
recipients with diseased native kidneys in situ supporting the performance of a
study in this patient group. Over 120 RDN procedures have been performed in the
UMCU so far with only few minor complications (mostly bleeding at the puncture
site).
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
- Age 18-75 years
- First kidney transplant in situ >6 months prior to randomization
- Urine measured creatinine clearance * 30 ml/min
- Radiological evidence for residual flow in the renal arteries indicating that they are accessible for the intervention
- Mean day-time systolic blood pressure of at least 135 mmHg (using ambulatory blood pressure monitoring) despite the use of at least 3 antihypertensive drugs, or with documented intolerance or contraindication for to 2 or more of the 4 major classes of antihypertensive drugs (ACEi/ARB, calcium channel blockers, betablockers and diuretics) thus being unable to be treated with 3 antihypertensives.
- Hemodynamically significant stenosis of the renal artery of the graft as a cause of therapy resistant hypertension has to be (have been) excluded (using MRI).
Exclusion criteria
- (Planned) pregnancy, lactation
- Life expectancy <1 year
- Contraindications for (relative) hypotensive episodes i.e. hemodynamically significant valvular disease, documented transient ischemic attacks or angina pectoris during relative hypotension
- Heart failure, NYHA class III-IV; chronic lung disease Gold III-IV
- Major complications during previous radiological interventions (i.e. allergy to contrast agent, cholesterol embolism)
- (Reno) vascular abnormalities in any part of the catheter access (including the aortic-iliac tract) route that impede the procedure of renal denervation
- Use of vitamine K antagonists or other (non-aspirin) form of anti- coagulatory therapy with an absolute indication (i.e. that cannot be temporarily stopped)
- Implantable cardioverter defibrillator (ICD) in situ
- Planned surgery within the next six months
- Drugs- or alcohol abuse
- Inability to give informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL52243.041.15 |