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Semin Respir Crit Care Med 2024; 45(04): 491-502
DOI: 10.1055/s-0044-1789240
Review Article

Epigenetic Mechanisms in Sepsis-Associated Acute Kidney Injury

Marco Fiorentino
1   Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro,” Bari, Italy
,
Reginald Philippe
2   Centre for Medical Sciences - CISMed, University of Trento, Trento, Italy
,
Carmen A. Palumbo
1   Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro,” Bari, Italy
,
Stefania Prenna
3   Department of Anesthesia and Intensive Care, Santa Chiara Hospital, APSS Trento, Trento, Italy
,
Vincenzo Cantaluppi
4   Nephrology and Kidney Transplantation Unit, Department of Translational Medicine (DIMET), University of Piemonte Orientale (UPO), “Maggiore della Carità” University Hospital, Novara, Italy
,
Silva De Rosa
2   Centre for Medical Sciences - CISMed, University of Trento, Trento, Italy
› Author Affiliations Funding This work was supported by Ministero dell'Università e delle Ricerche (PRIN2022-PNRR, P2022YKN4Y granted to M.F. and S.D.R., PRIN2022PF4NCA granted to V.C.).
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Abstract

Sepsis, the dysregulated immune response of the host to infections, leads to numerous complications, including multiple organ dysfunction with sepsis-associated acute kidney injury (SA-AKI) being a frequent complication associated with increased risk of mortality and the progression toward chronic kidney disease (CKD). Several mechanisms have been widely investigated in understanding the complex pathophysiology of SA-AKI, including hemodynamic alterations, inflammation, oxidative stress, and direct cellular injury driven by pathogens or cell-derived products (pathogen-associated molecular patterns and damage-associated molecular patterns). Despite advancements in the management of septic patients, the prognosis of SA-AKI patients remains significantly poor and is associated with high in-hospital mortality and adverse long-term outcomes. Therefore, recent research has focused on the early identification of specific SA-AKI endotypes and subphenotypes through epigenetic analysis and the use of potential biomarkers, either alone or in combination with clinical data, to improve prognosis. Epigenetic regulation, such as DNA methylation, histone modifications, and noncoding RNA modulation, is crucial in modulating gene expression in response to stress and renal injury in SA-AKI. At the same time, these modifications are dynamic and reversible processes that can alter gene expression in several pathways implicated in the context of SA-AKI, including inflammation, immune response, and tolerance status. In addition, specific epigenetic modifications may exacerbate renal damage by causing persistent inflammation or cellular metabolic reprogramming, leading to progression toward CKD. This review aims to provide a comprehensive understanding of the epigenetic characteristics that define SA-AKI, also exploring targeted therapies that can improve patient outcomes and limit the chronic progression of this syndrome.

Keywords

sepsis - acute kidney injury - epigenetics - inflammation - biomarkers - renal replacement therapy


Publication History

Article published online:
29 August 2024

© 2024. Thieme. All rights reserved.

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