Renal Sympathetic Denervation by Image-Guided Percutaneous Ethanol Injection – Histopathologic Characteristics, Efficacy and Safety

Abstract

Purpose Evaluation of the efficacy and safety of chemical renal denervation by image-guided periarterial ethanol injection in pigs with emphasis on histopathological characteristics.

Materials and Methods Unilateral renal periarterial ethanol injection under general anesthesia was performed in 16 animals with the contralateral kidney serving as the control. All interventions were performed in an open MRI system under real-time multiplanar guidance. In 10 pigs an ethanol-carbostesin contrast agent mixture was injected with amounts of 5 ml (6 animals, group I) and 10 ml (4 animals, group II). 6 pigs (group III) were treated with 10 ml of an ethanol-polyacrylic (2 %) mixture. Four weeks after treatment, all animals underwent MRI including MRA. After euthanasia, macroscopic and histologic examination of the kidneys, renal arteries and periarterial tissue was performed to assess nerve injury and potential side effects. Furthermore, the norepinephrine concentration (RTNEC) in the renal tissue was determined as a surrogate parameter of efficacy.

Results Histologic signs of nerval degeneration with various degrees of severity and circumferential distribution were found in all groups. Injury depths ranged up to 7.6 mm. In groups II and III the nerve count was significantly lower on the treated side. Renal artery stenosis was not observed in any pig. In all pigs of group II treatment resulted in neural degeneration with a mean RTNEC reduction of 53 % (p < 0.02). In groups I and III significant changes in RTNEC were not observed.

Conclusion Image-guided percutaneous periarterial ethanol injection was efficient and safe for renal denervation. The detected variations in histologic outcome underlined the importance of the preclinical optimization of the technique in order to maximize treatment effects in humans.

Key Points:

• Renal denervation by percutaneous periarterial ethanol injection is an effective and potentially safe procedure.

• The percutaneous approach is less prone to anatomical and procedural limitations compared to catheter-based procedures.

• The achievable nerve injury depth lies beyond those of current RFA-probes.

• Efficacy depends on amount, concentration, viscosity and periarterial distribution of the ethanol-mixture.

• Establishing an optimal balance between these parameters is mandatory for a maximum treatment effect at minimum risk for sensitive adjacent structures.

Citation Format

• Freyhardt P, Haage P, Walter A et al. Renal Sympathetic Denervation by Image-Guided Percutaneous Ethanol Injection – Histopathologic Characteristics, Efficacy and Safety. Fortschr Röntgenstr 2020; 192: 549 – 560

Zusammenfassung

Hintergrund Evaluation von Wirksamkeit und Sicherheit der chemischen renalen Denervation mittels bildgestützter periarterieller Ethanol-Injektion in Schweinen mit Schwerpunkt auf histopathologische Charakteristiken.

Material und Methoden In 16 narkotisierten Schweinen erfolgte eine 1-seitige periarterielle Ethanol-Injektion um eine Nierenarterie. Die unbehandelte Niere diente als Kontrolle. Alle Interventionen erfolgten in einem offenen MRT mit multiplanaren Echtzeit-Sequenzen zur Navigation. 10 Schweinen wurden 5 ml (6 Tiere, Gruppe I), respektive 10 ml (4 Tiere, Gruppe II) eines Ethanol-Carbostesin-Kontrastmittelgemisches injiziert. 6 Tiere (Gruppe III) wurden mit 10 ml eines Ethanol-Polyacryl (2 %) -Gemisches behandelt. 4 Wochen nach der Intervention wurde bei allen Tieren eine MRT-Untersuchung mit MRA durchgeführt. Nach erfolgter Euthanasie wurden eine makroskopische und histologische Untersuchung der Nieren, der Nierenarterien sowie des angrenzenden Bindegewebes zum Nachweis induzierter Nervendegenerationen und potenzieller Nebeneffekte durchgeführt. Als Surrogatparameter für die Wirksamkeit wurde die Noradrenalin-Konzentration des Nierengewebes (RTNEC) bestimmt.

Ergebnisse In den Präparaten aller Gruppen fanden sich histologische Zeichen einer periarteriellen Nervenschädigung unterschiedlicher Ausprägung und zirkumferentieller Verteilung. Die maximale Distanz geschädigter Nerven zur Gefäßintima betrug 7,6 mm. In den Gruppen II und III zeigte sich die Nervenanzahl auf der behandelten Seite signifikant reduziert im Vergleich zur Gegenseite. Nierenarterienstenosen fanden sich bei keinem Versuchstier. In Gruppe II wiesen alle Tiere einen signifikanten RTNEC-Abfall mit einer mittleren Reduktion von 53 % (p < 0,02) auf der behandelten Seite auf. In den Gruppen I und III wurde keine signifikante Veränderung der RTNEC beobachtet.

Schlussfolgerung Die bildgestützte, perkutane periarterielle Ethanol-Injektion zur renalen Denervation erwies sich als wirksam und sicher. Die beobachteten Variationen in der Ausprägung der induzierten histopathologischen Veränderungen unterstreichen die Notwendigkeit einer Optimierung der Technik mit dem Ziel eines maximalen Behandlungseffekts im Menschen.

Kernaussagen:

• Die renale Denervation durch perkutane periarterielle Ethanolinjektion ist eine effektive und potenziell sichere Prozedur.

• Der perkutane Zugang hat weniger anatomische und prozedurale Limitationen als endovaskuläre Verfahren.

• Die erzielbare Tiefe der Nervenschädigung ist größer als bei gängigen RFA-Elektroden.

• Die Wirksamkeit ist abhängig von Menge, Konzentration, Viskosität und periarterieller Verteilung des Ethanolgemischs.

• Eine optimale Balance zwischen diesen Parametern ist entscheidend für eine maximale Effektivität bei minimalem Risiko.

Key words

image-guided periarterial injection - interventional procedures - hypertension - renal denervation - ethanol sympathicolysis - sympathetic nerves

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