---
title: "Lactylation in Sepsis-Associated Acute Kidney Injury: Metabolic‑Epigenetic Mechanisms and Translat"
id: "pubmed-42658356"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42658356"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42658356/"
doi: "10.1007/s11033-026-12664-3"
published_at: "2026-08-27T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Lactylation in Sepsis-Associated Acute Kidney Injury: Metabolic‑Epigenetic Mechanisms and Translat
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42658356
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42658356/)
- **DOI:** [10.1007/s11033-026-12664-3](https://doi.org/10.1007%2Fs11033-026-12664-3)
- **Published At:** 2026-08-27T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Sepsis-associated acute kidney injury (SA-AKI) is a high‑mortality complication with few effective therapies. The reviewed article reframes lactate from a metabolic byproduct to an active **epigenetic** regulator via protein **lactylation**. - **Lactylation** is a posttranslational modification in which lactate covalently modifies lysine residues on proteins; this discovery shifts understanding of lactate’s role in pathobiology. - Lactylation operates through a dynamic **writer‑reader‑eraser** network that controls the installation, recognition, and removal of lactyl marks; the review summarizes this molecular basis. - In SA-AKI, lactylation functions as a central metabolic‑epigenetic hub, influencing multiple pathological processes including immune reprogramming, renal tubular cell fate, mitochondrial dysfunction, and microvascular integrity. - Immune effects include altering macrophage polarization and broader immune responses; these changes contribute to the inflammatory milieu of SA-AKI. - In tubular cells, lactylation is linked to mitochondrial dysfunction and altered cell fate decisions that can exacerbate injury or affect repair trajectories. - Lactylation effects are **cell‑type** and **spatiotemporally specific**, which helps explain apparently dual roles in both injury promotion and repair facilitation. - Specific lactylation marks, such as **H3K18 lactylation**, are proposed as candidate diagnostic biomarkers for SA-AKI based on their epigenetic signaling roles. - Targeting the lactylation axis offers novel precision‑therapy opportunities, although the review notes current research limitations and emphasizes the need to overcome these to achieve clinical translation. - The article is a review; experimental details, quantitative results, and clinical trial data were not reported in the abstract and thus are not included here.
## Clinical Analysis & Structured Key Points
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Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury [Yuqiu Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42658356)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-1 "College of Pharmaceutical Science, Zhejiang University of Technology, Zhejiang, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-2 "Hangzhou Institute of Medicine \(HIM\), Chinese Academy of Sciences, Hangzhou, China."), [Yan Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+Y&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China."), [Jiang Du](https://pubmed.ncbi.nlm.nih.gov/?term=Du+J&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China."), [Hang Wen](https://pubmed.ncbi.nlm.nih.gov/?term=Wen+H&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China."), [Xintong Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+X&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-4 "Postgraduate training base Alliance of Wenzhou Medical University \(Zhejiang cancer Hospital\), Hangzhou, China."), [Jian Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+J&cauthor_id=42658356)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-2 "Hangzhou Institute of Medicine \(HIM\), Chinese Academy of Sciences, Hangzhou, China."), [Yuxin Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-4 "Postgraduate training base Alliance of Wenzhou Medical University \(Zhejiang cancer Hospital\), Hangzhou, China."), [Ying Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+Y&cauthor_id=42658356)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-5 "Department of Physical Education, Zhejiang University of Science and Technology, Hangzhou, 310023, Zhejiang Province, China."), [Jianwei Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+J&cauthor_id=42658356)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-1 "College of Pharmaceutical Science, Zhejiang University of Technology, Zhejiang, China."), [Haibo Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+H&cauthor_id=42658356)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-2 "Hangzhou Institute of Medicine \(HIM\), Chinese Academy of Sciences, Hangzhou, China."), [Pingbo Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+P&cauthor_id=42658356)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-6 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China. zzmzkxpb@163.com.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#full-view-affiliation-7 "Hangzhou Institute of Medicine \(HIM\), Chinese Academy of Sciences, Hangzhou, China. zzmzkxpb@163.com.") Affiliations Expand ### Affiliations * 1 College of Pharmaceutical Science, Zhejiang University of Technology, Zhejiang, China. * 2 Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China. * 3 Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China. * 4 Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang cancer Hospital), Hangzhou, China. * 5 Department of Physical Education, Zhejiang University of Science and Technology, Hangzhou, 310023, Zhejiang Province, China. * 6 Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China. zzmzkxpb@163.com. * 7 Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China. zzmzkxpb@163.com. * PMID: **42658356** * DOI: [ 10.1007/s11033-026-12664-3 ](https://doi.org/10.1007/s11033-026-12664-3) Item in Clipboard Review # Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury Yuqiu Wang et al. Mol Biol Rep. 2026. Show details Display options Display options Format Abstract PubMed PMID Mol Biol Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mol+Biol+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Mol+Biol+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42658356/) . 2026 Aug 27;53(1):1464. doi: 10.1007/s11033-026-12664-3. ### Authors [Yuqiu Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42658356)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-1 "College of Pharmaceutical Science, Zhejiang University of Technology, Zhejiang, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-2 "Hangzhou Institute of Medicine \(HIM\), Chinese Academy of Sciences, Hangzhou, China."), [Yan Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+Y&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China."), [Jiang Du](https://pubmed.ncbi.nlm.nih.gov/?term=Du+J&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China."), [Hang Wen](https://pubmed.ncbi.nlm.nih.gov/?term=Wen+H&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China."), [Xintong Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+X&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-4 "Postgraduate training base Alliance of Wenzhou Medical University \(Zhejiang cancer Hospital\), Hangzhou, China."), [Jian Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+J&cauthor_id=42658356)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-2 "Hangzhou Institute of Medicine \(HIM\), Chinese Academy of Sciences, Hangzhou, China."), [Yuxin Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42658356)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-3 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-4 "Postgraduate training base Alliance of Wenzhou Medical University \(Zhejiang cancer Hospital\), Hangzhou, China."), [Ying Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+Y&cauthor_id=42658356)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-5 "Department of Physical Education, Zhejiang University of Science and Technology, Hangzhou, 310023, Zhejiang Province, China."), [Jianwei Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+J&cauthor_id=42658356)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-1 "College of Pharmaceutical Science, Zhejiang University of Technology, Zhejiang, China."), [Haibo Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+H&cauthor_id=42658356)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-2 "Hangzhou Institute of Medicine \(HIM\), Chinese Academy of Sciences, Hangzhou, China."), [Pingbo Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+P&cauthor_id=42658356)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-6 "Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China. zzmzkxpb@163.com.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42658356/#short-view-affiliation-7 "Hangzhou Institute of Medicine \(HIM\), Chinese Academy of Sciences, Hangzhou, China. zzmzkxpb@163.com.") ### Affiliations * 1 College of Pharmaceutical Science, Zhejiang University of Technology, Zhejiang, China. * 2 Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China. * 3 Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China. * 4 Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang cancer Hospital), Hangzhou, China. * 5 Department of Physical Education, Zhejiang University of Science and Technology, Hangzhou, 310023, Zhejiang Province, China. * 6 Department of Anesthesiology, Department of Pain management and Rehabilitation, Zhejiang Cancer Hospital, Zhejiang, 310022, Zhejiang, People's Republic of China. zzmzkxpb@163.com. * 7 Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China. zzmzkxpb@163.com. * PMID: **42658356** * DOI: [ 10.1007/s11033-026-12664-3 ](https://doi.org/10.1007/s11033-026-12664-3) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Sepsis-associated acute kidney injury is a lethal complication with limited therapeutic options. The discovery of protein lactylation, a novel modification where lactate modifies lysine residues, has redefined lactate from a metabolic waste product to a key epigenetic regulator. This review summarizes the role of lactylation as a central metabolic-epigenetic hub in SA-AKI pathogenesis. We detail its molecular basis, governed by a dynamic "writer-reader-eraser" network. In SA-AKI, lactylation orchestrates a multifaceted pathological cascade: it reprograms immune responses (e.g., altering macrophage polarization), disrupts tubular cell fate (e.g., inducing mitochondrial dysfunction), and compromises microvascular integrity. Its function exhibits cell-type and spatiotemporal specificity, explaining its dual roles in injury and repair. This mechanism provides a new framework for understanding SA-AKI and reveals promising translational avenues: specific lactylation marks (e.g., H3K18 lactylation) are potential diagnostic biomarkers, and targeting this axis offers novel strategies for precision therapy. Overcoming current research challenges is crucial for translating this knowledge into improved patient outcomes. **Keywords:** Inflammation; Lactylation; Metabolic reprogramming; SA-AKI. © 2026. The Author(s), under exclusive licence to Springer Nature B.V. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declrations. Competing interests: The authors declare no competing interests. ## References 1. 1. Wiersinga WJ, van der Poll T (2022) Immunopathophysiology of human sepsis. eBioMedicine 86:104363. - [DOI](https://doi.org/10.1016/j.ebiom.2022.104363) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/36470832/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/9783164/) 2. 1. Zarbock A, Nadim MK, Pickkers P et al (2023) Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup. Nat Rev Nephrol 19(6):401–417. - [DOI](https://doi.org/10.1038/s41581-023-00683-3) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/36823168/) 3. 1. White KC, Serpa-Neto A, Hurford R et al (2023) Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. A multicenter, observational study. Intensive Care Med 49(9):1079–1089. - [DOI](https://doi.org/10.1007/s00134-023-07138-0) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/37432520/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10499944/) 4. 1. Cho H, Jung J-Y, Yoon H-K et al (2023) Serum neutrophil gelatinase-associated lipocalin and lactate level during surgery predict acute kidney injury and early allograft dysfunction after liver transplantation. Sci Rep 13(1):8643. - [DOI](https://doi.org/10.1038/s41598-023-34372-9) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/37244919/) - [PMC](https://pmc.ncbi.nlm.nih.
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