Introduction: Sepsis is the leading contributor to acute kidney injury (AKI), responsible for 45-70% of AKI occurrences. Despite this, septic AKI is a highly multifactorial and complex condition, and our grasp of its pathogenesis is still not fully developed. Consequently, there remains a significant gap in effective diagnostic and therapeutic strategies for septic AKI.
Methods: In the in vitro experiments, BUMPT cells were exposed to lipopolysaccharides (LPS). In vivo experiments involved inducing sepsis in mice through administration of LPS injections. Additionally, in certain experiments, either a miR-455-5p mimic or an anti-miR-455-5p LAN was administered to the mice via injections into the tail vein. The mice were then sacrificed 24 h following LPS administration for subsequent analysis.
Results: We observed a significant elevation in miR-455-5p levels within renal tubular cells following LPS-induced septic AKI. Our investigation revealed that NF-κB plays a crucial role in the upregulation of miR-455-5p. Inhibition of NF-κB using TPCA-1 prevented the rise in miR-455-5p levels in BUMPT cells (mouse proximal tubular cells from Boston University) cultured in vitro. Chromatin immunoprecipitation assays confirmed that NF-κB directly interacts with the promoter region of the miR-455-5p gene in response to LPS treatment. Functionally, introducing miR-455-5p mimics intensified cell apoptosis, kidney damage, and the production of inflammatory cytokines, while silencing miR-455-5p had protective effects in septic mice. Notably, administering anti-miR-455-5p enhanced SOCS3 expression, whereas miR-455-5p mimics reduced SOCS3 levels following LPS exposure. Furthermore, our luciferase reporter assays demonstrated that SOCS3 is a direct target of miR-455-5p.
Conclusion: This study indicates an NF-κB/miR-455-5p/SOCS3 axis which can exacerbate kidney damage by enhancing renal inflammation. This process highlights potential therapeutic targets for managing septic AKI.
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http://dx.doi.org/10.1159/000541727 | DOI Listing |
Cureus
November 2024
Internal Medicine, Robert Wood Johnson (RWJ) Barnabas Health, Long Branch, USA.
Background: Septic shock is defined as sepsis with hypotension requiring vasopressors to maintain a mean arterial pressure above 65 mmHg and having a serum lactate level of more than 2 mmol/L despite adequate volume resuscitation as per the Sepsis-3 criteria. Continuous renal replacement therapy (CRRT) is commonly utilized in septic shock patients for the treatment of acute kidney injury as well as for modulating immune response and maintaining hemodynamic stability.
Methods: We looked at the National Inpatient Sample database in 2019.
Clin Sci (Lond)
December 2024
University of Utah Health, Salt Lake City, Utah, United States.
Septic acute kidney injury (AKI) is an important risk factor for developing chronic kidney disease (CKD). Hu antigen R (HuR) is recognized as a crucial modulator in inflammation. We hypothesized that elevated HuR contributes to the transition from septic AKI to CKD by promoting persistent inflammation and fibrosis, and inhibition of HuR may reverse septic kidney injury.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
Department of Emergency Medicine, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
Background: Sepsis is a systemic inflammatory response syndrome, with sepsis-associated acute kidney injury (SA-AKI) being a common complication. Insulin resistance (IR) is closely related to the stress response, inflammatory response, and severity of critical illness. The triglyceride-glucose body mass index (TyG-BMI) is a valuable tool for assessing IR.
View Article and Find Full Text PDFBMC Infect Dis
December 2024
Department of Intensive Care Medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China.
Background: Predicting mortality in sepsis-related acute kidney injury facilitates early data-driven treatment decisions. Machine learning is predicting mortality in S-AKI in a growing number of studies. Therefore, we conducted this systematic review and meta-analysis to investigate the predictive value of machine learning for mortality in patients with septic acute kidney injury.
View Article and Find Full Text PDFRev Esp Anestesiol Reanim (Engl Ed)
December 2024
Departamento de Farmacia, Clínica Universidad de Navarra, Pamplona, Universidad de Navarra, Spain.
Introduction: The independent association of vancomycin with Acute Kidney Injury (AKI) in the critically ill patient with sepsis or septic Shock is controversial. The aim of this study was to evaluate the incidence of AKI in a cohort of patients with sepsis or septic Shock with an adequate and strict monitoring of vancomycin, guided by the area under the concentration-time curve in relation to the minimum inhibitory concentration (AUC/MIC ratio).
Material And Methods: Retrospective cohort study on 106 patients admitted to the ICU with a diagnosis of sepsis or septic shock with vancomycin treatment, consecutively from January 2017 to December 2019.
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