Renal Nerve Ablation in Chronic Kidney Disease Patients

• ClinicalTrials.gov Identifier: NCT01442883
• Recruitment Status: Completed
• First Posted: September 29, 2011
• Last Update Posted: March 26, 2020
• Sponsor: University of Erlangen-Nürnberg Medical School
• Information provided by (Responsible Party): University of Erlangen-Nürnberg Medical School

Study Description

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

Condition or disease	Intervention/treatment
Hypertension; Chronic Kidney Disease	Device: Simplicity Catheter

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 27 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Understanding the Mechanisms of Progressive Decrease in Blood Pressure After Renal Nerve Ablation
• Actual Study Start Date: November 2010
• Actual Primary Completion Date: June 2019
• Actual Study Completion Date: June 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
treatment resistant hypertensives with CKD 3-5	Device: Simplicity Catheter; percutaneous selective renal sympathetic nerve ablation with the use of the Simplicity Catheter system

Outcome Measures

Primary Outcome Measures :

1. office BP [ Time Frame: baseline, 6 months ]
   Change in office blood pressure from baseline to 6 months post-renal nerve ablation
2. 24-h ABPM [ Time Frame: baseline, 6 months ]
   Change in 24 hour ambulatory blood pressure (ABPM) from baseline to 6 months post-renal nerve ablation
3. Magnetic resonance imaging (MRI) [ Time Frame: baseline, 6 months ]
   • 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
4. Albuminuria [ Time Frame: baseline, 6 months ]
   Change in urinary albumin/creatinine ratio from baseline to 6 months post renal nerve ablation (spot urine)
5. local RAS activity [ Time Frame: baseline, 6 months ]
   Change in urinary angiotensinogen concentration from the morning spot urine from baseline to 6 months post-renal nerve ablation
6. systemic RAS activity [ Time Frame: baseline, 6 months ]
   • 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
7. vascular structure and function of large and small arteries [ Time Frame: baseline, 6 months ]
   • 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

Secondary Outcome Measures :

1. BP [ Time Frame: 1 and 12 months ]
   • 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
2. local RAS activity [ Time Frame: 1 day and 1 months ]
   Change in urinary angiotensinogen concentration from the morning spot urine from baseline to 1 day and 1 months post-renal nerve ablation
3. systemic RAS activity [ Time Frame: 1 day and 1 months ]
   • 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
4. vascular structure and function of large and small arteries [ Time Frame: 12 months ]
   • 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
5. MRI [ Time Frame: 1 day, 1 and 12 months ]
   • 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

treatment resistant hypertensive adults with chronic kidney disease 3 - 5

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

Contacts and Locations

Locations

Germany

Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg

Erlangen, Germany, 91054

Joachim Weil

Lübeck, Germany

Sponsors and Collaborators

University of Erlangen-Nürnberg Medical School

Investigators

• Principal Investigator: Roland E Schmieder, MD; University of Erlangen-Nürnberg, Germany

More Information

Publications:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Erlangen-Nürnberg Medical School
• ClinicalTrials.gov Identifier: NCT01442883
• Other Study ID Numbers: RNA-CKD3-5
• First Posted: September 29, 2011
• Last Update Posted: March 26, 2020
• Last Verified: March 2020

Keywords provided by University of Erlangen-Nürnberg Medical School:

Treatment Resistant

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Renal Insufficiency