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, metabolic dysfunction-associated steatotic liver disease) is linked to sympathetic nervous system overactivity.
• Pharmacotherapy alone often provides suboptimal control for these conditions.
• Neuromodulatory strategies are being explored to address these complex diseases.

Purpose of the Study:

• To review the biological rationale, technical feasibility, and evidence for combined hepatic and renal denervation.
• To evaluate this approach as an investigational strategy for cardiometabolic disease.

Main Methods:

• Review of preclinical models and early first-in-human studies of celiac-hepatic denervation.
• Evaluation of emerging clinical data on hepatic and renal denervation.

Main Results:

• Preclinical models 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-controlled trials.

Conclusions:

• Combined hepatic and renal denervation is a translational, hypothesis-generating approach for cardiometabolic disease.
• Definitive conclusions on efficacy, durability, and mechanisms require rigorous randomized trials.
• Future research must focus on target engagement, safety, durability, and clinical relevance.