Renal Nerve Ablation in Chronic Kidney Disease Patients

NCT01442883 | Completed

• 1 other identifier: RNA-CKD3-5
• Study Type: observational
• Target: 27
• Locations: 1 country
• Sites: 2

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

Conditions

Hypertension; Chronic Kidney Disease

Keywords

Treatment Resistant

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (5)

• BP

  1 and 12 months

• local RAS activity

  1 day and 1 months

• systemic RAS activity

  1 day and 1 months

• vascular structure and function of large and small arteries

  12 months

• MRI

  1 day, 1 and 12 months

Study Arms (1)

treatment resistant hypertensives with CKD 3-5

Device: Simplicity Catheter

Interventions

Simplicity Catheter DEVICE

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

treatment resistant hypertensives with CKD 3-5

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

treatment resistant hypertensive adults with chronic kidney disease 3 - 5

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (2)

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

Erlangen, 91054, Germany

Location

Joachim Weil

Lübeck, Germany

Location

Related Publications (3)

• 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.

  PMID: 26873693 BACKGROUND

• 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.

  PMID: 26253780 BACKGROUND

• 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.

  PMID: 25923731 DERIVED

MeSH Terms

Conditions

Hypertension; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Roland E Schmieder, MD

  University of Erlangen-Nürnberg, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: September 29, 2011
• Study Start: November 1, 2010
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: March 26, 2020

Record last verified: 2020-03

Locations

DE (2)