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

Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and life-threatening complication in critically ill children, contributing to high mortality rates (up to 30%) and long-term renal dysfunction in pediatric intensive care units. This review synthesizes recent advances in the signalling pathways underlying SA-AKI, emphasizing pediatric-specific mechanisms, biomarkers, and therapeutic targets. This review covers inflammatory cascades via TLR/NF-κB leading to cytokine storms (IL-6, TNF-α); apoptosis and necrosis involving mitochondrial Bcl-2 dysregulation and OLFM4; and emerging processes like pyroptosis (NF-κB-mediated), metabolic reprogramming (choline deficiency and Nrf2-mitophagy), and novel routes such as cGAS-STING and TGF-β signalling. Biomarkers like urinary OLFM4, DKK3, NGAL, and serum suPAR, alanine, and Penkid enable early diagnosis and risk stratification, with models like PERSEVERE-II enhancing prognostic accuracy. Therapeutic strategies include fluid optimization, renal replacement therapies (CRRT, SLED-f), and pathway-targeted interventions such as choline supplementation, oXiris for cytokine removal, Humanin for immunomodulation, and investigational cGAS-STING inhibitors. Despite progress, challenges persist in translating animal models to pediatric trials and addressing heterogeneity. Integrating multi-omics and precision medicine holds promise for improving outcomes, underscoring the need for multicenter studies in children.