β-hydroxybutyrate: A Renoprotective Hormone In Polycystic Kidney Disease

Area of Science:

• Nephrology
• Metabolic Disorders
• Genetics

Background:

• Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent genetic kidney disease with limited treatment options.
• Disease progression in ADPKD is highly variable, influenced by nutritional, lifestyle, and environmental factors.
• ADPKD is increasingly recognized as a cellular metabolic disorder characterized by impaired mitochondrial function and glucose reliance.

Purpose of the Study:

• To review the current understanding of Ketogenic Metabolic Therapy (KMT) and beta-hydroxybutyrate (BHB) for ADPKD.
• To discuss the potential of KMT and BHB as safe, non-invasive, disease-modifying interventions for ADPKD.
• To highlight BHB's role as a renoprotective signaling hormone in ADPKD.

Main Methods:

• Literature review of preclinical and clinical studies on KMT and BHB in ADPKD.
• Analysis of the metabolic derangements in ADPKD, including mitochondrial dysfunction and glucose metabolism.
• Examination of the signaling pathways and pleiotropic effects of BHB.

Main Results:

• KMT, including ketogenic diets and BHB supplementation, shows promising outcomes in preclinical and early clinical ADPKD studies.
• BHB acts as a key renoprotective mediator, offering alternative energy and exerting signaling effects.
• BHB's signaling functions may reduce cyst proliferation, inflammation, oxidative stress, and fibrosis, while improving mitochondrial function.

Conclusions:

• BHB is a critical renoprotective signaling hormone with potential therapeutic benefits for ADPKD.
• KMT interventions targeting metabolic vulnerabilities represent a promising, safe, and non-invasive strategy for ADPKD.
• Restoring endogenous ketogenesis or supplementing with BHB may counteract the detrimental effects of modern lifestyle patterns on kidney health in ADPKD.