Evaluation of the Biomarkers HMGB1 and IL-6 as Predictors of Mortality in Cirrhotic Patients with Acute Kidney Injury

Gomes, Célio Geraldo de Oliveira; Andrade, Marcus V.; Guedes, Ludmila Resende; Rocha, Henrique Carvalho; Guimarães, Ricardo Queiroz; Carvalho, Fernando Antônio Castro; Vilela, Eduardo García

doi:10.1155/2020/2867241

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…The above-mentioned findings suggested that HMGB1 was mainly secreted by podocytes and maybe partly released by apoptotic podocytes. Previous studies have shown that HMGB1 is a late inflammatory factor and secreted by immune cells and injured cells [ 22 , 23 ]. To investigate the role of HMGB1 in podocytes, HMGB1 expression in podocytes was suppressed by HMGB1 siRNA.…”

Section: Discussionmentioning

confidence: 99%

Release of HMGB1 in Podocytes Exacerbates Lipopolysaccharide-Induced Acute Kidney Injury

Gao

Lü

Chen

2021

Mediators of Inflammation

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Objective. Acute kidney injury (AKI) usually occurs during sepsis. Inflammation factors, such as high-mobility group box 1 (HMGB1), are dramatically upregulated under septic conditions. In our current work, the functions of HMGB1 in AKI were explored. Methods. An AKI model was induced by the lipopolysaccharide (LPS) challenge in C57 mice. Podocytes were challenged by LPS for different durations. Subsequently, podocytes transfected with HMGB1 siRNA were exposed to LPS for 24 h. The expressions of supernatant HMGB1 and cellular active caspase-3 were examined by Western blotting analysis. To explore the effect of HMGB1 on tubular epithelial cells (TECs), HK-2 cells were exposed to HMGB1 at various concentrations for 24 h. Epithelial-mesenchymal transition (EMT) of HK-2 cells was evaluated by Western blotting analysis. Mitochondrial division and apoptosis of HK-2 cells were assessed by MitoTracker Red and Western blotting analysis, respectively. Results. Compared with the sham control group, the expression of HMGB1 was increased in the kidney of AKI mice. Moreover, the expression of supernatant HMGB1 was increased in LPS-challenged podocytes compared with the control group. Knockdown of HMGB1 attenuated LPS-induced podocyte injury. Besides, EMT in TECs was triggered by HMGB1. Mitochondrial damage and apoptosis of HK-2 cells exposed to HMGB1 were markedly elevated compared with the control group. Conclusions. Collectively, HMGB1 release in podocytes was induced by LPS, subsequently leading to exacerbated AKI.

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Section: Discussionmentioning

confidence: 99%

Release of HMGB1 in Podocytes Exacerbates Lipopolysaccharide-Induced Acute Kidney Injury

Gao

Lü

Chen

2021

Mediators of Inflammation

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“…Inflammatory cytokines such as IL-6 are secreted to a much greater extent in the face of serious injuries or infections that manifest systemically with haemodynamic instability or more important metabolic disorders. In these situations, IL-6 is closely related to shock, multiple organ failure and death [28].…”

Section: Discussionmentioning

confidence: 99%

Performance of High Mobility Protein Group 1 and Interleukin-6 as Predictors of Outcomes Resulting from Variceal Bleeding in Patients with Advanced Chronic Liver Disease

et al. 2021

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Variceal bleeding is a serious complication in cirrhotic patients and is related to increased expression of inflammatory mediators that accentuate circulatory dysfunction. The study aims to evaluate the performance of high mobility protein group 1 (HMG1) and interleukin-6 (IL-6) as predictors of acute kidney injury (AKI), infection and death in these patients. Fifty patients who were diagnosed with advanced chronic liver disease with variceal bleeding were included. The mean age was 52.8 ± 10.8 years, and 33 (66%) were male. Twenty-one (42%) patients were classified as Child-Pugh C, 21 (42%) Child-Pugh B and 8 (16%) Child-Pugh A. The mean HMG1 serum level was 2872.36 pg/mL ± 2491.94, and the median IL-6 serum level was 47.26 pg/mL (0-1102.4). In AKI, the serum level of HMG1 that performed best on the ROC curve was 3317.9 pg/mL. The IL-6 serum level was not associated with AKI. HMG1 and IL-6 cut-off values that better predicted infection were 3317.9 pg/mL and 72.9 pg/mL, and for mortality, the values were 2668 pg/mL and 84.5 pg/mL, respectively. In multivariate analysis, the variables that were associated with AKI and infection outcomes were model for end-stage liver disease and HMG1. Infections were related to the risk of death. Clinical and laboratory variables related to the outcomes were identified. Serum levels of HMG1 were associated with AKI and infection and had

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“…In addition, HMGB1 has been recognized as a danger signal involved in the pathogenesis of various inflammatory diseases, malignancies, and injury [ 57 , 58 , 59 ]. On the contrary to these functional roles, HMGB1 is also useful as a biomarker in various diseases [ 60 , 61 ]. HMGB1 is noticed in serum in patients with severe cutaneous adverse reactions [ 62 , 63 ].…”

Section: Clinical Sign and Biomarker For Drug Eruptionmentioning

confidence: 99%

Diagnostic Tools and Biomarkers for Severe Drug Eruptions

Yoshioka

Sawada

Nakamura

2021

IJMS

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In accordance with the development of human technology, various medications have been speedily developed in the current decade. While they have beneficial impact on various diseases, these medications accidentally cause adverse reactions, especially drug eruption. This delayed hypersensitivity reaction in the skin sometimes causes a life-threatening adverse reaction, namely Stevens-Johnson syndrome and toxic epidermal necrolysis. Therefore, how to identify these clinical courses in early time points is a critical issue. To improve this problem, various biomarkers have been found for these severe cutaneous adverse reactions through recent research. Granulysin, Fas ligands, perforin, and granzyme B are recognized as useful biomarkers to evaluate the early onset of Stevens-Johnson syndrome and toxic epidermal necrolysis, and other biomarkers, such as miRNAs, high mobility group box 1 protein (HMGB1), and S100A2, which are also helpful to identify the severe cutaneous adverse reactions. Because these tools have been currently well developed, updates of the knowledge in this field are necessary for clinicians. In this review, we focused on the detailed biomarkers and diagnostic tools for drug eruption and we also discussed the actual usefulness of these biomarkers in the clinical aspects based on the pathogenesis of drug eruption.

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Evaluation of the Biomarkers HMGB1 and IL-6 as Predictors of Mortality in Cirrhotic Patients with Acute Kidney Injury

Cited by 9 publications

References 35 publications

Release of HMGB1 in Podocytes Exacerbates Lipopolysaccharide-Induced Acute Kidney Injury

Release of HMGB1 in Podocytes Exacerbates Lipopolysaccharide-Induced Acute Kidney Injury

Performance of High Mobility Protein Group 1 and Interleukin-6 as Predictors of Outcomes Resulting from Variceal Bleeding in Patients with Advanced Chronic Liver Disease

Diagnostic Tools and Biomarkers for Severe Drug Eruptions

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