The results of this study will give better insights in the role of ADMA in the development of systemicendothelial dysfunction and the relation with mild renal insufficiency.
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Basal renal perfusion, fractional change in renal perfusion after intrarenal
L-NMMA infusion, arterial en venous ADMA, SDMA (symmetric dimethylarginine) and
L-arginine concentrations and renal elimination of systemic ADMA, SDMA and
L-arginine
Secondary outcome
Microalbuminuria, creatinin clearance, blood pressure, plasma LDL (low density
lipoproteins), HDL (high density lipoproteins), triglycerides and total
cholesterol concentrations
Background summary
ADMA (asymmetrical dimethylarginine) is an endogenous inhibitor of nitric oxide
(NO), the most important determinant for endothelial dependent vasodilatation.
ADMA plasma concentrations are elevated in several cardiovascular risk
populations, including patients with essential hypertension and/or kidney
insufficiency. Recent clinical studies demonstrated that ADMA has also a
pronounced impact on (primary NO-regulated) renal perfusion. Furthermore,
medication like angiotensine-II-receptorblokkers (ARB) and statines lower ADMA
concentrations and improve endothelial dependent dilation.
Hypothesis: ADMA plasma concentrations are higher in persons with mild renal
insufficiency compared to persons with normal kidney function. ADMA plasma
concentrations are inversely proportional to renal perfusion and endothelial
nitric oxide (NO) availibility in the kidney. Medical treatment with statins
and/or angiotensin II receptor blockers (ARB) will reduce ADMA plasma
concentrations, improves kidney perfusion and NO availibility.
Study objective
The results of this study will give better insights in the role of ADMA in the
development of systemic
endothelial dysfunction and the relation with mild renal insufficiency.
Study design
The study is a singleblind, randomized controled intervention trail. Sixty nine
patients will be randomized in 3 intervention groups and treated during 3 weeks
with eprosartan, rosuvastatin or both till the renal angiography.
Intervention
The intervention will consist of a three-week treatment period with eprosartan
600mg and/or rosuvastatin
20 mg. During the renal angiography, L-NMMA will be intrarenally administered
after the regular 133 Xenon perfusion measurement, followed by an additional
133 Xenon perfusion measurement and blood sampling.
Study burden and risks
We expect from participants that they (besides the clinical indicated
diagnostic investigations) 1) take the prescribed medication during 3 weeks
before the renal angiography, 2) go through an additional 133 Xenon perfusion
measurement during 20 minutes and 3) 2 blood samples (a. renalis and v.
renalis) will be collected from the catheter during the renal angiography 4) a
non-invasive Laser Doppler Flow measurement will be performed during 15
minutes. Besides all these measurements, 2 venous blood samples of 5 mL will be
collected.
There is a risk on side effects due to the study
medication, however this risk is very small. Since the pretreatment period is
only 3 weeks, participants have no direct benefit by participating in this
study other than the quantification of renal flow due to treatment with a ARB
and/or statin.
P. Debyelaan 25
6202 AZ Maastricht
NL
P. Debyelaan 25
6202 AZ Maastricht
NL
Listed location countries
Age
Inclusion criteria
o Hypertension
(Office blood pressure >140 and/or >90 mmHg or ABPM blood pressure:
>125 and/or >80 mmHg)
o Age: 18-75 jaar
o Creatinin clearance of 60-90 mL/min
(Cockcroft-Gault formula)
o Renal angiography indicated, based on the following criteria:
- Refractory hypertension
- Accelerating or malignant hypertension
- Elevating serum creatinin after an ACE-inhibitor or ARB
- Kidney size < 8 cm measured by ultrasound
- Unexplained hypokalemia
- Abdominal or
renal souffle
- Manifestations of atherosclerosis
elsewhere
- *Flash* oedema
Exclusion criteria
o Primary kidney diseases or urological complaints
o Diabetes Mellitus
o Chronic inflammatory diseases
o Recent infections (< 3 weeks)
o Unilateral or bilateral renal artery stenosis
o Fibromuscular dysplasia (FMD)
o Contraindication for ARB or statin
o Use of > 4 units alcohol a day
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2008-004743-10-NL |
| CCMO | NL24152.068.08 |