Metabolic Reprogramming and Host Tolerance: A Novel Concept to Understand Sepsis-Associated AKI

Area of Science:

• Nephrology
• Immunology
• Cellular Metabolism

Background:

• Sepsis frequently causes acute kidney injury (AKI), increasing mortality and chronic kidney disease risk.
• Mechanisms of sepsis-associated AKI remain unclear, particularly how tubular epithelial cells (TECs) survive sepsis-induced stress.
• The concept of 'tolerance' in host defense, distinct from 'resistance,' highlights tissue's capacity to limit injury.

Purpose of the Study:

• To review the role of metabolic reprogramming in TECs as a defense strategy during sepsis.
• To explore how TEC metabolic adaptation contributes to a 'tolerance' mechanism against sepsis-induced kidney injury.
• To discuss the involvement of mitochondrial function and regulatory nodes in this cellular response.

Main Methods:

• Literature review focusing on cellular and molecular mechanisms of sepsis-associated AKI.
• Analysis of studies investigating TEC responses to sepsis.
• Synthesis of current knowledge on metabolic reprogramming and mitochondrial roles in kidney injury.

Main Results:

• TECs may employ metabolic reprogramming as a crucial defense mechanism during sepsis.
• This metabolic adaptation likely operates via a 'tolerance' strategy, limiting tissue damage rather than eliminating pathogens.
• Mitochondria and specific regulatory pathways are central to orchestrating this protective cellular response.

Conclusions:

• TEC metabolic reprogramming is a key component of the host's defense against sepsis-induced AKI.
• Understanding these tolerance mechanisms, particularly mitochondrial roles, opens new avenues for therapeutic interventions.
• Targeting TEC metabolism could offer novel strategies to prevent or treat sepsis-associated AKI.