Clinical trial NCT01442883: Renal Nerve Ablation in Chronic Kidney Disease Patients
Official title: Understanding the Mechanisms of Progressive Decrease in Blood Pressure After Renal Nerve Ablation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypertension
Chronic Kidney Disease
Keywords: Treatment Resistant
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2011-09-29
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: treatment resistant hypertensive adults with chronic kidney disease 3 - 5

Brief summary: In patients with treatment resistent hypertension renal nerve ablation emerged as an effective interventional approach of treating hypertensive disease with a progressively increasing fall in blood pressure. Decreased activity of the sympathetic nervous system is one of the major underlying pathogenetic mechanism of the fall in blood pressure but the precise mechanisms that causes the fall in blood pressure in the short-term and, in particular, long-term remains elusive. The objective of the study is to understand the pathogenetic mechanisms of renal denervation beyond the reduced activity of the sympathetic nervous system. In 100 hypertensive patients most advanced technology will be applied, before and repeatedly after renal denervation, throughout the follow-up period of 1 year. Systemic activity of the renin angiotensin aldosterone system, renal perfusion (by MRI spin labelling technique), local activity of the renin angiotensin system in the kidney (urinary angiotensinogen concentrations), sodium excretion and total sodium content (23 Na-MRI technique) and vascular remodelling of small (retinal arterioles 50 - 150 µm) and large arteries (carotid - femoral pulse wave velocity and augmentation index, both measured over 24 hours) will be assessed. Identification of the pathogenetic mechanisms involved in the fall in blood pressure after renal denervation may help to identify those hypertensive patients that profit most from renal nerve ablation in terms of blood pressure reduction.

The investigators propose the following hypotheses why a progressive decrease in blood pressure happens, in addition to the decreased activity of the central nervous system, after renal nerve ablation:

Short term effects:

A)Preservation of renal function and perfusion B)Reduction of local RAS activity in the kidney C)Exaggerated sodium excretion immediately after renal nerve ablation

Long term effects:

D)Decrease of total sodium content after 6 and 12 months. E)Improvement of vascular wall properties after 6 and 12 months

Detailed description: In patients with treatment resistent hypertension renal nerve ablation emerged as an effective interventional approach of treating hypertensive disease with a progressively increasing fall in blood pressure. Decreased activity of the sympathetic nervous system is one of the major underlying pathogenetic mechanism of the fall in blood pressure but the precise mechanisms that causes the fall in blood pressure in the short-term and, in particular, long-term remains elusive. The objective of the study is to understand the pathogenetic mechanisms of renal denervation beyond the reduced activity of the sympathetic nervous system. In 100 hypertensive patients most advanced technology will be applied, before and repeatedly after renal denervation, throughout the follow-up period of 1 year. Systemic activity of the renin angiotensin aldosterone system, renal perfusion (by MRI spin labelling technique), local activity of the renin angiotensin system in the kidney (urinary angiotensinogen concentrations), sodium excretion and total sodium content (23 Na-MRI technique) and vascular remodelling of small (retinal arterioles 50 - 150 µm) and large arteries (carotid - femoral pulse wave velocity and augmentation index, both measured over 24 hours) will be assessed. Identification of the pathogenetic mechanisms involved in the fall in blood pressure after renal denervation may help to identify those hypertensive patients that profit most from renal nerve ablation in terms of blood pressure reduction.

Eligibility criteria: Inclusion Criteria:

* treatment resistant hypertension
* chronic kidney disease 3 - 5
* male of female aged over 18 years
* written informed consent
* agreement to attend all study visits as planned in the protocol

Exclusion Criteria:

* any contraindications for MRI
* claustrophobia
* strabismus
* severe ocular diseases
* history of epilepsia

Primary outcomes:
measure: office BP
timeFrame: baseline, 6 months
measure: 24-h ABPM
timeFrame: baseline, 6 months
measure: Magnetic resonance imaging (MRI)
timeFrame: baseline, 6 months
measure: Albuminuria
timeFrame: baseline, 6 months
measure: local RAS activity
timeFrame: baseline, 6 months
measure: systemic RAS activity
timeFrame: baseline, 6 months
measure: vascular structure and function of large and small arteries
timeFrame: baseline, 6 months
Secondary outcomes:
measure: BP
timeFrame: 1 and 12 months
measure: local RAS activity
timeFrame: 1 day and 1 months
measure: systemic RAS activity
timeFrame: 1 day and 1 months
measure: vascular structure and function of large and small arteries
timeFrame: 12 months
measure: MRI
timeFrame: 1 day, 1 and 12 months
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg
city: Lübeck
country: Germany
facility: Joachim Weil
Study officials:
affiliation: University of Erlangen-Nürnberg, Germany
name: Roland E Schmieder, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmieder RE, Ott C, Schmid A, Friedrich S, Kistner I, Ditting T, Veelken R, Uder M, Toennes SW. Adherence to Antihypertensive Medication in Treatment-Resistant Hypertension Undergoing Renal Denervation. J Am Heart Assoc. 2016 Feb 12;5(2):e002343. doi: 10.1161/JAHA.115.002343.
citation: Schmid A, Schmieder R, Lell M, Janka R, Veelken R, Schmieder RE, Uder M, Ott C. Mid-Term Vascular Safety of Renal Denervation Assessed by Follow-up MR Imaging. Cardiovasc Intervent Radiol. 2016 Mar;39(3):426-32. doi: 10.1007/s00270-015-1192-2. Epub 2015 Aug 8.
citation: Ott C, Mahfoud F, Schmid A, Toennes SW, Ewen S, Ditting T, Veelken R, Ukena C, Uder M, Bohm M, Schmieder RE. Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension. J Hypertens. 2015 Jun;33(6):1261-6. doi: 10.1097/HJH.0000000000000556.