Metabolic acidosis: new insights from mouse models

Area of Science:

• Nephrology
• Physiology
• Molecular Biology

Background:

• Metabolic acidosis disrupts pH homeostasis, linked to kidney defects or overproduction of metabolic acids.
• Chronic metabolic acidosis can lead to osteomalacia, nephrocalcinosis, and urolithiasis.
• In end-stage renal disease, metabolic acidosis is an independent risk factor for increased morbidity.

Purpose of the Study:

• To review recent insights into kidney mechanisms for regulating and adapting acid excretion.
• To highlight progress in understanding ammonia synthesis/excretion, acidosis adaptation, and acidosis sensing in the kidney.
• To explore the pathophysiology of inherited and acquired renal acid handling errors.

Main Methods:

• Utilizing genetic mouse models to study renal acid-base balance.
• Employing messenger RNA and proteome profiling technologies.
• Analyzing screening data to identify key proteins and networks.

Main Results:

• New understanding of mechanisms governing kidney ammonia synthesis and excretion.
• Insights into adaptive physiological responses within the kidney during acidosis.
• Identification of pathways involved in the kidney's sensing of acidosis.
• Elucidation of the pathophysiology underlying renal acid handling disorders.

Conclusions:

• Genetic mouse models and advanced profiling technologies underscore the role of acid-base transporters.
• A complex metabolic and regulatory network is vital for maintaining systemic acid-base balance by the kidney.