Metabolic reprogramming in septic acute kidney injury: pathogenesis and therapeutic implications

Area of Science:

• Nephrology
• Immunology
• Metabolic Biology

Background:

• Sepsis-associated acute kidney injury (S-AKI) is a severe complication with high mortality.
• The precise pathogenesis of S-AKI, particularly the role of metabolic changes, remains incompletely understood.
• Metabolic reprogramming, akin to the Warburg effect in cancer, is implicated in S-AKI.

Purpose of the Study:

• To review the current understanding of metabolic reprogramming in S-AKI.
• To focus on the specific cell types involved in S-AKI metabolic shifts.
• To identify potential therapeutic targets related to metabolic reprogramming in S-AKI.

Main Methods:

• Literature review of studies on S-AKI pathogenesis.
• Analysis of metabolic changes in inflammatory and renal cells during sepsis.
• Examination of mitochondrial dynamics and cellular energy metabolism in S-AKI.

Main Results:

• During early sepsis, inflammatory and renal cells (macrophages, neutrophils, tubular epithelial cells) exhibit aerobic glycolysis for inflammation and resilience.
• As sepsis progresses, these cells shift to oxidative phosphorylation, promoting anti-inflammatory responses and functional recovery.
• Mitochondrial dynamics and metabolic reprogramming are central to energy alterations in S-AKI.

Conclusions:

• Metabolic reprogramming is a key feature of S-AKI pathogenesis.
• Understanding cell-specific metabolic shifts is crucial for S-AKI management.
• Targeting metabolic reprogramming pathways presents a promising therapeutic strategy for S-AKI.