Metabolic reprogramming rewires aberrant immune responses to drive endothelial dysfunction in Kawasaki disease: a narrative review.

Background and Objective: Kawasaki disease (KD) is a systemic pediatric vasculitis characterized by dysregulated immune activation and substantial risk of coronary artery lesions. Emerging evidence suggests metabolic reprogramming is a critical link between immune responses and endothelial dysfunction during KD progression. This review aims to provide an integrated overview of metabolic alterations in KD pathogenesis, focusing on clinical observations, mechanistic insights, and experimental evidence. Methods: A literature search was conducted using PubMed and Web of Science to identify studies published up to July 2026, combining "Kawasaki disease" with terms related to metabolism and metabolic pathways, including metabolites, glucose, glycolysis, amino acids, lipids, fatty acid oxidation, succinic acid, the tricarboxylic acid (TCA) cycle, nitric oxide, urine, gut microbiota, mouse models, and therapeutic strategies. Relevant clinical, experimental, and mechanistic studies were reviewed and synthesized. Key Content and Findings: Accumulating evidence indicates extensive metabolic remodeling in KD, including enhanced glycolysis, disrupted lipid metabolism and fatty acid oxidation, altered amino acid metabolism, and TCA cycle perturbations. These abnormalities are closely linked to immune activation, mitochondrial dysfunction, oxidative stress, and vascular inflammation. KD mouse models further support metabolic reprogramming, marked by altered tryptophan and amino acid metabolism, lipid metabolism, and lactate production. Notably, kynurenine pathway activation with reduced tryptophan availability is associated with inflammatory amplification and mitochondrial impairment. Beyond host-derived changes, gut microbiota dysbiosis and its metabolites appear to correlate with immune responses and disease severity. However, clinical translation of these metabolic signatures into reliable biomarkers or therapeutic targets remains limited. Conclusions: This review highlights metabolic reprogramming as a key interface linking immune dysregulation, endothelial injury, and vascular complications in KD. Metabolic abnormalities may act not merely as consequences of inflammation but as active regulators of vascular dysfunction and disease progression. Significant gaps remain in establishing causal relationships between specific metabolic alterations and KD pathogenesis. Future studies integrating multicenter cohorts with cellular, multi-omics, and animal model approaches, particularly centered on the metabolic-immune-vascular injury axis, will be essential for identifying novel biomarkers and therapeutic strategies.