Cardiometabolic Multimorbidity and Sympathetic Overactivity: Translational Rationale for Combined Hepatic-Renal...

Area of Science:

• Cardiovascular Medicine
• Nephrology
• Hepatology
• Neurology

Background:

• Cardiometabolic multimorbidity (type 2 diabetes, hypertension, fatty liver disease) is linked to sympathetic overactivity.
• Pharmacotherapy alone often provides suboptimal control for these conditions.
• Neuromodulatory strategies are being explored to address underlying sympathetic dysfunction.

Purpose of the Study:

• To review the rationale, feasibility, and evidence for combined hepatic and renal denervation.
• To evaluate this investigational approach for managing cardiometabolic diseases.
• To identify the need for further clinical validation.

Main Methods:

• Review of preclinical models and early first-in-human studies.
• Evaluation of biological rationale and technical feasibility.
• Assessment of emerging clinical data on celiac-hepatic denervation.

Main Results:

• Preclinical data suggest multiorgan denervation can modulate sympathetic activity and metabolic pathways.
• Early human studies indicate celiac-hepatic denervation is feasible with acceptable short-term safety.
• Current human evidence is limited by small sample sizes and lack of sham controls.

Conclusions:

• Combined hepatic and renal denervation is a translational, hypothesis-generating strategy for cardiometabolic disease.
• Definitive conclusions on efficacy, durability, and mechanisms require more robust evidence.
• Rigorous randomized trials are essential to establish clinical relevance and safety.