Renal Nerve Ablation in Chronic Kidney Disease Patients

Hypertension Clinical Trial

Official title:

Understanding the Mechanisms of Progressive Decrease in Blood Pressure After Renal Nerve Ablation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01442883
• Other study ID #: RNA-CKD3-5
• Status: Completed
• Start date: November 2010
• Est. completion date: June 2019

Study information

• Verified date: March 2020
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Hypertension
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Device:
• Simplicity Catheter
percutaneous selective renal sympathetic nerve ablation with the use of the Simplicity Catheter system

Locations

Country	Name	City	State
Germany	Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg	Erlangen
Germany	Joachim Weil	Lübeck

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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. — View 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). pii: e002343. doi: 10.1161/JAHA.115.002343. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	office BP	Change in office blood pressure from baseline to 6 months post-renal nerve ablation	baseline, 6 months
Primary	24-h ABPM	Change in 24 hour ambulatory blood pressure (ABPM) from baseline to 6 months post-renal nerve ablation	baseline, 6 months
Primary	Magnetic resonance imaging (MRI)	change in total sodium content measured by MRI from baseline to 6 months post-renal nerve ablation; change in renal perfusion measured by MRI spin labelling technique from baseline to 6 months post-renal nerve ablation	baseline, 6 months
Primary	Albuminuria	Change in urinary albumin/creatinine ratio from baseline to 6 months post renal nerve ablation (spot urine)	baseline, 6 months
Primary	local RAS activity	Change in urinary angiotensinogen concentration from the morning spot urine from baseline to 6 months post-renal nerve ablation	baseline, 6 months
Primary	systemic RAS activity	change in sodium, potassium and creatinine from baseline to 6 months post-renal nerve ablation; change in aldosterone excretion from baseline to 6 months post-renal nerve ablation; change in sodium / potassium ratio from baseline to 6 months post-renal nerve ablation; change in plasma renin activity and angiotensin II concentration at least 30 minutes of rest in a supine position and immediately after standing from baseline to 6 months post-renal nerve ablation	baseline, 6 months
Primary	vascular structure and function of large and small arteries	change in flow-mediated vasodilation (FMD) from baseline to 6 months post-renal nerve ablation; change in scanning laser Doppler flowmetry (SLDF) from baseline to 6 months post-renal nerve ablation; change in pulse wave analysis (PWA) from baseline to 6 months post-renal nerve ablation; change in pulse wave velocity from (PWV) baseline to 6 months post-renal nerve ablation; change in urinary albumine creatinine ratio (UACR) of the morning spot urine sample from baseline to 6 months post-renal nerve ablation	baseline, 6 months
Secondary	BP	change in office blood pressure from baseline to 1 and 12 months post-renal nerve ablation; change in 24 hour ambulatory blood pressure from baseline to 1 and 12 months post-renal nerve ablation	1 and 12 months
Secondary	local RAS activity	Change in urinary angiotensinogen concentration from the morning spot urine from baseline to 1 day and 1 months post-renal nerve ablation	1 day and 1 months
Secondary	systemic RAS activity	change in sodium, potassium and creatinine from baseline to 1 day and 1 months post-renal nerve ablation; change in albuminuria from baseline to 1 and 12 months post-renal nerve ablation; change in aldosterone excretion from baseline to 1 day and 1 months post-renal nerve ablation; change in sodium / potassium ratio from baseline to 1 day and 1 months post-renal nerve ablation; change in plasma renin activity and angiotensin II concentration at least 30 minutes of rest in a supine position and immediately after standing from baseline to 1 day and 1 months post-renal nerve ablation	1 day and 1 months
Secondary	vascular structure and function of large and small arteries	change in flow-mediated vasodilation (FMD) from baseline to 12 months post-renal nerve ablation; change in scanning laser Doppler flowmetry (SLDF) from baseline to 12 months post-renal nerve ablation; change in pulse wave analysis (PWA) from baseline to 12 months post-renal nerve ablation; change in pulse wave velocity from (PWV) baseline to 12 months post-renal nerve ablation; change in urinary albumine creatinine ratio (UACR) of the morning spot urine sample from baseline to 12 months post-renal nerve ablation	12 months
Secondary	MRI	change in total sodium content measured by MRI from baseline to 12 months post-renal nerve ablation; change in renal perfusion measured by MRI spin labelling technique from baseline to 1 day and 1 months post-renal nerve ablation	1 day, 1 and 12 months