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

SA-AKI in critically ill children has a high mortality rate, and while biomarkers and therapeutic strategies are discussed, specific clinical evidence for interventions like Humanin is lacking.

Summary and findings

This review addresses the signaling pathways related to sepsis-associated acute kidney injury (SA-AKI) in children, focusing on pediatric-specific mechanisms and potential therapeutic targets. It discusses biomarkers for diagnosis and risk stratification, as well as various therapeutic strategies including Humanin for immunomodulation. No specific numeric findings or doses were reported in the abstract.

Abstract

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.

Key findings

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Limitations

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