Renal Nerve Ablation in Chronic Kidney Disease Patients

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

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

Study Overview

• Status: Completed
• Conditions: Hypertension; Chronic Kidney Disease
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg
  • Lübeck, Germany
    • Joachim Weil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

treatment resistant hypertensive adults with chronic kidney disease 3 - 5

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
office BP	Change in office blood pressure from baseline to 6 months post-renal nerve ablation	baseline, 6 months
24-h ABPM	Change in 24 hour ambulatory blood pressure (ABPM) from baseline to 6 months post-renal nerve ablation	baseline, 6 months
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
Albuminuria	Change in urinary albumin/creatinine ratio from baseline to 6 months post renal nerve ablation (spot urine)	baseline, 6 months
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Principal Investigator: Roland E Schmieder, MD, University of Erlangen-Nürnberg, Germany

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2010
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 28, 2011
• First Posted (Estimate): September 29, 2011

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Treatment Resistant
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: RNA-CKD3-5