Research Progress on Signalling Pathways Related to Sepsis-Associated Acute Kidney Injury in Children

Area of Science:

• Pediatric Nephrology
• Critical Care Medicine
• Molecular Biology

Background:

• Sepsis-associated acute kidney injury (SA-AKI) is a critical condition in critically ill children, leading to significant mortality and long-term kidney problems.
• Understanding the specific pediatric mechanisms of SA-AKI is crucial for developing effective treatments.

Purpose of the Study:

• To review recent advancements in SA-AKI signalling pathways, focusing on pediatric-specific aspects.
• To highlight novel biomarkers and therapeutic targets for SA-AKI in children.

Main Methods:

• Comprehensive literature review of signalling pathways (TLR/NF-κB, apoptosis, pyroptosis, metabolic reprogramming, cGAS-STING, TGF-β).
• Analysis of emerging and established biomarkers for diagnosis and risk stratification.
• Evaluation of current and investigational therapeutic strategies.

Main Results:

• Identified key pathways including inflammatory cascades, apoptosis/necrosis, pyroptosis, metabolic reprogramming, and novel signalling routes.
• Highlighted promising biomarkers (e.g., urinary OLFM4, NGAL; serum suPAR) and prognostic models (PERSEVERE-II).
• Discussed therapeutic interventions ranging from supportive care to pathway-targeted agents (choline, Humanin, cGAS-STING inhibitors).

Conclusions:

• SA-AKI pathogenesis is multifaceted, involving inflammation, cell death, and metabolic shifts.
• Early diagnosis and risk stratification are enhanced by novel biomarkers and models.
• Targeted therapies and precision medicine approaches show potential but require further pediatric-specific research and multicenter validation.