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Review Open Access

Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)

  • Authors:
    • Lu Xu
    • Wei Jiang
    • Lin Song
    • Jing Wang
    • Jiangquan Yu
    • Ruiqiang Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Critical Care Medicine, The Yangzhou Clinical College of Xuzhou Medical University, Yangzhou, Jiangsu 225001, P.R. China, Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 78
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    Published online on: January 30, 2026
       https://doi.org/10.3892/ijmm.2026.5749
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Abstract

Sepsis is a life‑threatening clinical syndrome characterized by a dysregulated host immune response to infection, with its pathogenesis closely linked to the aberrant activation and dysfunction of various immune cells. The kidney is among the most vulnerable organs in sepsis. The development of acute kidney injury (AKI) in sepsis, referred to as sepsis‑associated AKI (SA‑AKI), is often associated with significantly increased mortality. Despite its clinical impact, specific and effective therapies for SA‑AKI remain scarce. Increasing evidence highlights that complex intrarenal inflammatory processes, primarily driven by diverse immune cell populations, are central to the onset and progression of SA‑AKI. The present review provides a comprehensive analysis of the roles of both innate and adaptive immune cells, such as macrophages, neutrophils, dendritic cells, natural killer cells, natural killer T (NKT) cells, B cells and T cells, in SA‑AKI and explores potential therapeutic strategies, offering a theoretical foundation and insights for the development of more effective prevention and treatment approaches.

View Figures

Figure 1

Immune response in SA-AKI. SA-AKI,
sepsis-associated acute kidney injury; NK, natural killer; NKT,
natural killer T; TLR, Toll-like receptor; DAMPs, damage-associated
molecular patterns; IFN-γ, interferon-γ; FasL, Fas ligand; PD-L1,
programmed death-ligand 1; TNF-α, Tumor Necrosis Factor-α; IL,
interleukin; ROS, reactive oxygen species; FoxP3, forkhead box P3;
TGF-β, transforming growth factor-β; BTK, Bruton's tyrosine kinase;
CXCL1/2, C-X-C motif chemokine ligand 1/2; MHC, major
histocompatibility complex; TCR, T-cell antigen receptor; CD73,
ecto-5'-nucleotidase.

Figure 2

Role of macrophages in
sepsis-associated acute kidney injury. NF-κB, nuclear factor-κB;
JAK, Janus kinase; STAT, signal transducer and activator of
transcription; mTOR, mammalian target of rapamycin; IGF1,
insulin-like growth factor 1; IGF1R, insulin-like growth factor 1
receptor; IL, interleukin; TGF, transforming growth factor; Ser,
Serine; A2AR, adenosineA2A receptor; P38, mitogen-activated protein
kinase 14; MMT, macrophage-to-myofibroblast transition; α-KG,
α-ketoglutarate; iNOS, inducible nitric oxide synthase.

Figure 3

Role of neutrophils in
sepsis-associated acute kidney injury. DAMPs, damage-associated
molecular patterns; PAMPs, pathogen-associated molecular patterns;
NK, natural killer; TEM, transendothelial migration; rTEM, reverse
transendothelial migration; ROS, reactive oxygen species; HMGB1,
high mobility group box 1 protein; NETs, neutrophil extracellular
traps; NE, neutrophil elastase; ICAM-1, intercellular adhesion
molecule-1.

Figure 4

Role of dendritic cells in SA-AKI.
SA-AKI, sepsis-associated acute kidney injury; LPS,
lipopolysaccharide; BTK, Bruton's tyrosine kinase; Syk, spleen
tyrosine kinase; TLR, Toll-like receptor; TCR, T-cell antigen
receptor; OXPHOS, oxidative phosphorylation.

Figure 5

Role of NK cells in sepsis-associated
acute kidney injury. RIC, renal intrinsic cell; ADCC,
antibody-dependent cellular cytotoxicity; NK, natural killer;
IFN-γ, interferon-γ; TNF, tumor necrosis factor; FasL, Fas ligand;
IL-10, interleukin-10.

Figure 6

Role of adaptive immune cells in
sepsis-associated acute kidney injury. Tregs, regulatory T cells;
Ado, adenosine; AR, adenosine receptor; IL, interleukin; TGF-β,
transforming growth factor-β; PD-L1, programmed death-ligand 1;
Gln, glutamine; FoxP3, forkhead box P3; IFNγ, interferon-γ.
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Spandidos Publications style
Xu L, Jiang W, Song L, Wang J, Yu J and Zheng R: <p>Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)</p>. Int J Mol Med 57: 78, 2026.
APA
Xu, L., Jiang, W., Song, L., Wang, J., Yu, J., & Zheng, R. (2026). <p>Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)</p>. International Journal of Molecular Medicine, 57, 78. https://doi.org/10.3892/ijmm.2026.5749
MLA
Xu, L., Jiang, W., Song, L., Wang, J., Yu, J., Zheng, R."<p>Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)</p>". International Journal of Molecular Medicine 57.4 (2026): 78.
Chicago
Xu, L., Jiang, W., Song, L., Wang, J., Yu, J., Zheng, R."<p>Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)</p>". International Journal of Molecular Medicine 57, no. 4 (2026): 78. https://doi.org/10.3892/ijmm.2026.5749
Copy and paste a formatted citation
x
Spandidos Publications style
Xu L, Jiang W, Song L, Wang J, Yu J and Zheng R: <p>Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)</p>. Int J Mol Med 57: 78, 2026.
APA
Xu, L., Jiang, W., Song, L., Wang, J., Yu, J., & Zheng, R. (2026). <p>Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)</p>. International Journal of Molecular Medicine, 57, 78. https://doi.org/10.3892/ijmm.2026.5749
MLA
Xu, L., Jiang, W., Song, L., Wang, J., Yu, J., Zheng, R."<p>Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)</p>". International Journal of Molecular Medicine 57.4 (2026): 78.
Chicago
Xu, L., Jiang, W., Song, L., Wang, J., Yu, J., Zheng, R."<p>Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review)</p>". International Journal of Molecular Medicine 57, no. 4 (2026): 78. https://doi.org/10.3892/ijmm.2026.5749
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