{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T14:34:48Z","timestamp":1787150088690,"version":"build-2736575974"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Sepsis-associated acute kidney injury (SA-AKI) is a prevalent, life-threatening sepsis complication with high mortality, prolonged organ support dependence, and scarce targeted therapies. Beyond being an anaerobic glycolysis byproduct, lactate serves as a critical circulating carbon source, mitochondrial fuel, redox regulator, signaling molecule, and lysine lactylation (Kla) substrate. Its multifaceted functions are vital to SA-AKI pathogenesis, which involves systemic lactate overload, impaired lactate clearance, renal metabolic reprogramming, and abnormal immune activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review synthesizes up-to-date evidence to systematically elucidate lactate and Kla mechanisms in SA-AKI. We hierarchically integrate findings from systemic sepsis metabolism and renal tubular lactate handling to cell-specific Kla modifications, aiming to clarify their distinct roles in SA-AKI progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Specific Kla sites (H3K18la, Fis1 K20la, LDHB K156la, Ezrin K263la, HMGB1 lactylation, ALDH2 K68la) mediate SA-AKI pathologies including mitochondrial dysfunction, tubular death, endothelial injury, and cGAS-STING\/NLRP3-neutrophil extracellular trap activation. Lactate accumulation, acidosis, transport, oxidation, metabolic routing, and Kla are mechanistically distinct rather than uniformly harmful. Lactate\/pyruvate metabolism exerts context-dependent injurious or adaptive effects across kidney disease models, modulated by cell type, injury phase, and metabolic reserve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Lactate- and Kla-targeted strategies are promising for SA-AKI treatment yet require rigorous clinical validation. Blood lactate level and clearance are reliable clinical prognostic biomarkers, whereas Kla signatures remain investigational. Balanced understanding of lactate-Kla biology will refine precision diagnostic and therapeutic strategies for SA-AKI, advancing translational clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1899336","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T14:16:46Z","timestamp":1787149006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactylation in sepsis-associated acute kidney injury: regulatory mechanisms and therapeutic prospects"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiahui","family":"Zheng","sequence":"first","affiliation":[{"name":"Graduate School, Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Graduate School, Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41419-023-05952-4","article-title":"PDHA1 hyperacetylation-mediated lactate overproduction promotes sepsis-induced acute kidney injury via Fis1 lactylation","volume":"14","author":"An","year":"2023","journal-title":"Cell Death Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5591","DOI":"10.1113\/jphysiol.2009.178350","article-title":"Cell\u2013cell and intracellular lactate shuttles","volume":"587","author":"Brooks","year":"2009","journal-title":"J. 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