HMGB1 and acute kidney injury: Similarly, a cascade involving HMGB1 lactylation-mediated NETosis through the mtDNA-cGAS-STING pathway has been identified in murine SA-AKI, where elevated blood lactate initiates H3K18 lactylation in macrophages, leading to HMGB1 lactylation and secretion, which in turn induces mtDNA leakage in neutrophils and activates cGAS-STING to promote NET formation (104, 105).