Immunoregulatory mechanism of acute kidney injury in sepsis: A Narrative Review

Sun, Shujun; Chen, Rui; Dou, Xiaoke; Dai, Maosha; Long, Junhao; Wu, Yan; Lin, Yun

doi:10.1016/j.biopha.2022.114202

Cited by 17 publications

(7 citation statements)

References 155 publications

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“…Sepsis is the most common cause of mortality in intensive care units ( 91 ). Lung and kidney involvement is relatively common in sepsis, and dysfunction of these organs is associated with poor survival outcome ( 92 , 93 ). Therefore, it has become increasingly important to identify agents that have therapeutic or protective effects on the lungs and kidney during sepsis.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation

Yavuz,

Küçük,

Ergörün

et al. 2024

Exp Ther Med

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Sepsis is a systemic inflammatory response syndrome that develops in the host against microorganisms. This response develops away from the primary infection site and results in end-organ damage. The present study aimed to investigate the protective and therapeutic effects on lung and kidney tissue of silymarin (S) and dexmedetomidine (DEX) applied 1 h before and after sepsis induced by the cecal ligation and puncture (CLP) method in rats. A total of 62 rats was randomly divided into eight groups: i) Control (n=6); ii) cecal perforation (CLP; n=8); iii) S + CLP (n=8; S + CLP; S administered 1 h before CPL); iv) CLP + S (n=8; S administered 1 h after CLP); v) DEX + CLP (n=8; D + CLP; DEX administered 1 h before CLP); vi) CLP + D (n=8; DEX administered 1 h after CLP); vii) SD + CLP (n=8; S and DEX administered 1 h before CLP) and viii) CLP + SD (n=8; S and DEX administered 1 h after CLP). After the cecum filled with stool, it was tied with 3/0 silk under the ileocecal valve and the anterior surface of the cecum was punctured twice with an 18-gauge needle. A total of 100 mg/kg silymarin and 100 µg/kg DEX were administered intraperitoneally to the treatment groups. Lung and kidney tissue samples were collected to evaluate biochemical and histopathological parameters. In the histopathological examination, all parameters indicating kidney injury; interstitial edema, peritubular capillary dilatation, vacuolization, ablation of tubular epithelium from the basement membrane, loss of brush border in the proximal tubule epithelium, cell swelling and nuclear defragmentation; were increased in the CLP compared with the control group. Silymarin administration increased kidney damage, including ablation of tubular epithelium from the basement membrane, compared with that in the CLP group. DEX significantly reduced kidney damage compared with the CLP and silymarin groups. The co-administration of DEX + silymarin decreased kidney damage, although it was not as effective as DEX-alone. To conclude, intraperitoneal DEX ameliorated injury in CLP rats. DEX + silymarin partially ameliorated injury but silymarin administration increased damage. As a result, silymarin has a negative effects with this dosage and DEX has a protective effect. In the present study, it was determined that using the two drugs together had a greater therapeutic effect than silymarin and no differences in the effects were not observed any when the application times of the agents were changed.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation

Yavuz,

Küçük,

Ergörün

et al. 2024

Exp Ther Med

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“…The infiltration of WBC into the injured kidneys via the circulatory system triggers the release of inflammatory mediators, including cytokines and chemical factors. These inflammatory substances contribute to kidney damage and exacerbate the injury [ 30 , 31 ]. These infiltrating WBC play a crucial role in AKI.…”

Section: Discussionmentioning

confidence: 99%

Machine learning-based prediction model of acute kidney injury in patients with acute respiratory distress syndrome

Wei,

Zhang,

Dong

et al. 2023

BMC Pulm Med

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Background Acute kidney injury (AKI) can make cases of acute respiratory distress syndrome (ARDS) more complex, and the combination of the two can significantly worsen the prognosis. Our objective is to utilize machine learning (ML) techniques to construct models that can promptly identify the risk of AKI in ARDS patients. Method We obtained data regarding ARDS patients from the Medical Information Mart for Intensive Care III (MIMIC-III) and MIMIC-IV databases. Within the MIMIC-III dataset, we developed 11 ML prediction models. By evaluating various metrics, we visualized the importance of its features using Shapley additive explanations (SHAP). We then created a more concise model using fewer variables, and optimized it using hyperparameter optimization (HPO). The model was validated using the MIMIC-IV dataset. Result A total of 928 ARDS patients without AKI were included in the analysis from the MIMIC-III dataset, and among them, 179 (19.3%) developed AKI after admission to the intensive care unit (ICU). In the MIMIC-IV dataset, there were 653 ARDS patients included in the analysis, and among them, 237 (36.3%) developed AKI. A total of 43 features were used to build the model. Among all models, eXtreme gradient boosting (XGBoost) performed the best. We used the top 10 features to build a compact model with an area under the curve (AUC) of 0.850, which improved to an AUC of 0.865 after the HPO. In extra validation set, XGBoost_HPO achieved an AUC of 0.854. The accuracy, sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and F1 score of the XGBoost_HPO model on the test set are 0.865, 0.813, 0.877, 0.578, 0.957 and 0.675, respectively. On extra validation set, they are 0.724, 0.789, 0.688, 0.590, 0.851, and 0.675, respectively. Conclusion ML algorithms, especially XGBoost, are reliable for predicting AKI in ARDS patients. The compact model maintains excellent predictive ability, and the web-based calculator improves clinical convenience. This provides valuable guidance in identifying AKI in ARDS, leading to improved patient outcomes.

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“…An increasing number of studies have demonstrated that excessive inflammatory cascade reaction in septic AKI is one of the main causes of kidney damage 6,7 . Macrophages are an important component of innate and adaptive immunity, which play a crucial role in regulating inflammatory response in septic AKI 8,9 .…”

Section: Introductionmentioning

confidence: 99%

“…An increasing number of studies have demonstrated that excessive inflammatory cascade reaction in septic AKI is one of the main causes of kidney damage. 6 , 7 Macrophages are an important component of innate and adaptive immunity, which play a crucial role in regulating inflammatory response in septic AKI. 8 , 9 Due to the plasticity and diversity of macrophages, macrophages can differentiate into two phenotypes, type M1 (classically activated) and type M2 (alternatively activated), which together maintain immune homeostasis within the body.…”

Section: Introductionmentioning

confidence: 99%

Dehydroandrographolide facilitates M2 macrophage polarization by downregulating DUSP3 to inhibit sepsis‐associated acute kidney injury

Shao,

Yu,

Cai

2024

Immunity Inflam & Disease

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BackgroundSepsis is perceived as lethal tissue damage and significantly increases mortality in combination with acute kidney injury (AKI). M2 macrophages play important roles in the secretion of anti‐inflammatory and tissue repair mediators. We aimed to study the role of Dehydroandrographolide (Deh) in sepsis‐associated AKI in vitro and in vivo through lipopolysaccharide (LPS)‐induced macrophages model and cecal ligation and puncture‐induced AKI mice model, and to reveal the mechanism related to M2 macrophage polarization.MethodsEnzyme‐linked immunosorbent assay kits were used to assess the levels of inflammatory factors. Expression of markers related to M1 macrophages and M2 macrophages were analyzed. Additionally, dual specificity phosphatase 3 (DUSP3) expression was tested. Cell apoptosis was evaluated by flow cytometry analysis and terminal‐deoxynucleotidyl transferase‐mediated nick end labeling staining. Moreover, renal histological assessment was performed by using hematoxylin and eosin staining.ResultsDeh reduced inflammation of THP‐1‐derived macrophages exposed to LPS. Besides, Deh induced the polarization of M1 macrophages to M2 and downregulated DUSP3 expression in THP‐1‐derived macrophages under LPS conditions. Further, DUSP3 overexpression reversed the impacts of Deh on the inflammation and M2 macrophages polarization of THP‐1‐derived macrophages stimulated by LPS. Additionally, human proximal tubular epithelial cells (HK‐2) in the condition medium from DUSP3‐overexpressed THP‐1‐derived macrophages treated with LPS and Deh displayed decreased viability and increased apoptosis and inflammation. The in vivo results suggested that Deh improved the renal function, ameliorated pathological injury, induced the polarization of M1 macrophages to M2, suppressed inflammation and apoptosis, and downregulated DUSP3 expression in sepsis‐induced mice.ConclusionDeh facilitated M2 macrophage polarization by downregulating DUSP3 to inhibit septic AKI.

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Immunoregulatory mechanism of acute kidney injury in sepsis: A Narrative Review

Cited by 17 publications

References 155 publications

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation

Machine learning-based prediction model of acute kidney injury in patients with acute respiratory distress syndrome

Dehydroandrographolide facilitates M2 macrophage polarization by downregulating DUSP3 to inhibit sepsis‐associated acute kidney injury

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