Identification of hantavirus infection by Western blot assay and TaqMan PCR in patients hospitalized with acute kidney injury

AbstractBackground and aimAcute kidney injury (AKI) is a common complication of sepsis. Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays a vital role in various diseases, including AKI. This study aimed to investigate the function and mechanism of NEAT1 in sepsis-induced AKI.Materials and methodsA septic AKI model was established by treating HK-2 cells with lipopolysaccharide (LPS). The levels of NEAT1 and miR-22-3p were measured by quantitative real-time PCR. Cell apoptosis was assessed by flow cytometry. The levels of apoptosis-related protein and autophagy-related factors were examined by the western blot assay. An enzyme-linked immunosorbent assay was used to calculate the contents of inflammatory factors. The interaction between NEAT1 and miR-22-3p was validated by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay. The levels of nuclear factor (NF)-κB pathway-related proteins were evaluated by the western blot assay.ResultsNEAT1 was upregulated, while miR-22-3p was downregulated in patients with sepsis and in LPS-stimulated HK-2 cells. LPS treatment triggered cell apoptosis, autophagy, and inflammatory response in HK-2 cells. NEAT1 knockdown attenuated LPS-induced cell injury. NEAT1 modulated LPS-triggered cell injury by targeting miR-22-3p. Furthermore, NEAT1 regulated the NF-κB pathway by modulating miR-22-3p.ConclusionDepletion of NEAT1 alleviated sepsis-induced AKI via regulating the miR-22-3p/NF-κB pathway.

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Hemorrhagic fever with renal syndrome with concurrent aortic dissection: a case report

10.21203/rs.3.rs-49633/v1 ◽

2020 ◽

Author(s):

Fengqi Qiu ◽

Congcong Li ◽

Jianya Zhou

Keyword(s):

Acute Kidney Injury ◽

Aortic Dissection ◽

Kidney Injury ◽

Hemorrhagic Fever ◽

Sudden Onset ◽

High Fever ◽

Hantaan Virus ◽

Hantavirus Infection ◽

Microvascular Damage ◽

Stanford B

Abstract Background Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses presenting with high fever, hemorrhage, acute kidney injury. Microvascular injury and hemorrhage in mucus was often observed in patients with hantavirus infection. Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically. We present a previously unreported case of hemorrhagic fever with concurrent Stanford B aortic dissection. Case presentation: A 56-year-old man complained of high fever, generalized body ache, with decreased platelet counts of 10 × 10^9/L and acute kidney injury. The ELISA test for Hantaan virus of IgM and IgG antibodies were both positive. During the convalescent period, he complained sudden onset acute chest pain radiating to the back and the CTA revealed an aortic dissection of the descending aorta extending to iliac artery. He was diagnosed with Hemorrhagic fever with renal syndrome and Stanford B aortic dissection. The patient recovered completely after surgery with other support treatments. Conclusion We present a case of HFRS complicated with aortic dissection,and no study has reported the association of HFRS with aortic disease. However, we suppose that hantavirus infection not only cause microvascular damage but may be risk factor for acute macrovascular detriment. A causal relationship has yet to be confirmed.

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Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

Pathogens ◽

10.3390/pathogens9080615 ◽

2020 ◽

Vol 9 (8) ◽

pp. 615

Author(s):

Paula Mantula ◽

Johanna Tietäväinen ◽

Jan Clement ◽

Onni Niemelä ◽

Ilkka Pörsti ◽

...

Keyword(s):

Acute Kidney Injury ◽

Acute Phase ◽

Kidney Injury ◽

University Hospital ◽

Hantavirus Infection ◽

Puumala Virus ◽

Disappearance Rate ◽

Time Points ◽

Albumin Excretion ◽

Fever Onset

Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20–200 μg/min), while 57% presented with severely increased albuminuria (cU-Alb >200 μg/min). Median cU-Alb was 311 μg/min (range 2.2–6460) ≤7 days after fever onset, 235 μg/min (range 6.8–5479) at 8–13 days and 2.8 μg/min (range 0.5–18.2) at 14–20 days. After that, only one of the measurements showed albuminuria (35.4 μg/min at day 44). At six months, the median cU-Alb was 2.0 μg/min (range 0.6–14.5). Albuminuria makes a flash-like appearance in PUUV infection and returns rapidly to normal levels within 2–3 weeks after fever onset. In the case of AKI, this is a unique phenomenon.

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PROTECTIVE EFFECT OF PHYLLANTHUS EMBLICA EXTRACT PREVENT CONTRAST-INDUCED ACUTE KIDNEY INJURY IN RATS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i10.35042 ◽

2019 ◽

pp. 197-201

Author(s):

SUPRANEE KONGKHAM ◽

ADIS TASANARONG ◽

ARUNPORN ITHARAT

Keyword(s):

Acute Kidney Injury ◽

Western Blot ◽

Blot Analysis ◽

Western Blot Analysis ◽

Kidney Injury ◽

Saline Control ◽

Phyllanthus Emblica ◽

Rt Pcr ◽

Expression Levels ◽

Apoptotic Effect

Objective: The objective of the study was to investigate the anti-apoptosis effect of the extract from Phyllanthus emblica (PE) for the prevention of contrast-induced acute kidney injury (CI-AKI). Methods: Male Sprague Dawley rats were given saline (control) or PE extracts (500 mg/kg/day) for 5 days before the induction of CI-AKI. Renal tissues were collected for an evaluation of gene expression and immunohistochemistry (IHC). To indicate anti-apoptotic effect, the expression levels of Bax, Bcl-2, and caspase in kidney were also determined, using real-time polymerase chain reaction (RT-PCR) and Western blot analysis. Results: In the CI-AKI group, RT-PCR and Western blot analysis revealed that the expression levels of Bax and cleaved-caspase-3 were upregulated in the CI-AKI group, whereas the expression of Bcl-2 was downregulated. However, the pre-treatment with PE increased Bcl-2 expression. Moreover, decreased cleaved-caspases-3 activity was also detected using IHC. Conclusion: These findings suggested that pretreatment with PE extract provided the anti-apoptotic effect against CI-AKI in the rat model.

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Coagulopathy in Acute Puumala Hantavirus Infection

Viruses ◽

10.3390/v13081553 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1553

Author(s):

Sirpa Koskela ◽

Satu Mäkelä ◽

Tomas Strandin ◽

Antti Vaheri ◽

Tuula Outinen ◽

...

Keyword(s):

Acute Kidney Injury ◽

Platelet Count ◽

Disseminated Intravascular Coagulation ◽

Inflammatory Mediators ◽

Kidney Injury ◽

Hemorrhagic Fever ◽

Endothelial Activation ◽

Hantavirus Infection ◽

Increased Risk ◽

Low Platelet Count

Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS), also called nephropathia epidemica (NE), which is mainly endemic in Europe and Russia. The clinical features include a low platelet count, altered coagulation, endothelial activation, and acute kidney injury (AKI). Multiple connections between coagulation pathways and inflammatory mediators, as well as complement and kallikrein–kinin systems, have been reported. The bleeding symptoms are usually mild. PUUV-infected patients also have an increased risk for disseminated intravascular coagulation (DIC) and thrombosis.

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ADAMTS-13-Regulated Nrf2 Signaling Inhibits Ferroptosis to Ameliorate Cisplatin-Induced Acute Kidney Injury

10.21203/rs.3.rs-679682/v1 ◽

2021 ◽

Author(s):

Xiaoyan Meng ◽

Wenjing Huang ◽

Weiwei Mo ◽

Tingting Shu ◽

Haoqiang Yang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Western Blot ◽

Kidney Injury ◽

Renal Tissue ◽

Tubular Damage ◽

Nrf2 Signaling Pathway ◽

Function Impairment ◽

Pas Staining ◽

Related Proteins ◽

The Relationship

Abstract Background: ADAMTS-13 plays an important role in acute kidney injury (AKI), but the mechanism of cisplatin (CP) induced AKI remains unclear. Ferroptosis is increased in CP-induced AKI, and ADAMTS13 levels are associated with ferritin expression. In this article, we will explore the relationship between the three.Methods： After CP induction, mice were given 0.1 and 0.3nmol/kg ADAMTS-13, and then Scr and BUN were detected by the kits. The pathological changes of renal tissue were observed by staining with HE and PAS staining, and Western blot detected the expressions of KIM1 and NGAL in renal tissu. Perl's staining detected iron deposition in renal tissues, the kits detected iron levels, and western blot detected the expression of ferroptosis related proteins. Then the mechanism was further explored by adding ferroptosis inhibitors Ferrostatin 1 (Fer-1) and iron supplements Fe. The expression of Nrf2 pathway related proteins were detected by Western blot.Results: ADAMTS13 alleviated CP-induced ferroptosis in AKI mice with renal function impairment and tubular damage. Fer-1partially reversed CP-induced AKI, and Fe exacerbated this effect. ADAMTS13 alleviated CP-induced inflammatory response and oxidative stress in AKI mice, during which the Nrf2 signaling pathway was abnormal.Conclusion:ADAMTS-13-regulated Nrf2 signaling inhibits ferroptosis to ameliorate CP-induced AKI.

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Haematuria is a marker for the severity of acute kidney injury but does not associate with thrombocytopenia in acute Puumala hantavirus infection

Infectious Diseases ◽

10.1080/23744235.2017.1358461 ◽

2017 ◽

Vol 49 (11-12) ◽

pp. 840-846 ◽

Cited By ~ 6

Author(s):

Tuula K. Outinen ◽

Paula Mantula ◽

Outi K. Laine ◽

Ilkka Pörsti ◽

Antti Vaheri ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Hantavirus Infection

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Eleutheroside B Protects against Acute Kidney Injury by Activating IGF Pathway

Molecules ◽

10.3390/molecules24213876 ◽

2019 ◽

Vol 24 (21) ◽

pp. 3876 ◽

Cited By ~ 2

Author(s):

Hongmei Zang ◽

Qin Yang ◽

Jun Li

Keyword(s):

Acute Kidney Injury ◽

Western Blot ◽

Inflammatory Cytokines ◽

Periodic Acid ◽

Specific Treatment ◽

Renal Dialysis ◽

Kidney Injury ◽

Rapid Decline ◽

Mrna Levels ◽

Eleutheroside B

Acute kidney injury (AKI) is a common, complex, and severe clinical syndrome characterized by rapid decline in renal function, combined with tissue damage. Currently, the prevention and treatment of AKI are focused on symptomatic treatment, rather than treating the underlying causes. Therefore, there is no specific treatment to prevent renal injury except for renal dialysis. In this study, we used cisplatin-induced AKI mouse and human kidney-2 (HK-2) cell models to evaluate the renal protective effect of eleutheroside B, an active compound in traditional Chinese medicines. MTT assay was used to detect the effect of eleutheroside B on proliferation of human HK-2 cells in presence and in absence of cisplatin. Western blot and immunostaining were used to detect the protein level of kidney injury molecule-1 (KIM-1), cleaved caspase-3, receptor-interacting protein kinase (RIPK)-1, and RIPK-3. Real-time PCR was used to detect the mRNA levels of chemokines (like monocyte chemotactic protein 1, MCP-1) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). Flow cytometry assay was used to detect apoptosis of HK-2 cells. In vivo results showed that eleutheroside B reduced the increase in serum creatinine and blood urea nitrogen (BUN) levels in the AKI model. Periodic acid-Schiff staining and Western blot analysis of KIM-1 showed that eleutheroside B alleviated tubular cell injury. Further, eleutheroside B reduced macrophage infiltration and production of inflammatory cytokines, inhibited the activation of nuclear factor (NF)-κB, and inhibited apoptosis and programmed necrosis. The mechanism may be that eleutheroside B can activate the insulin-like growth factor (IGF) pathway and its downstream pathway by downregulating the expression of IGFBP-7, thus promoting cell proliferation. Therefore, our results suggest that eleutheroside B is a potential drug for AKI treatment.

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P0521TICAGRELOR PROTECTS KIDNEY FROM SEPSIS INDUCED ACUTE KIDNEY INJURY THROUGH ADENOSINE DEPENDENT WAY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0521 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yuhan Cao ◽

Qiancheng Xu ◽

Yuwei Wang ◽

Cong Fu

Keyword(s):

Acute Kidney Injury ◽

Serum Creatinine ◽

Western Blot ◽

Receptor Antagonist ◽

Adenosine Receptor ◽

Kidney Injury ◽

Tunel Staining ◽

Adenosine Receptor Antagonist ◽

Tnf Α ◽

Pas Staining

Abstract Background and Aims Sepsis induced acute kidney injury (AKI) is common in intensive care unit in multiple organ failure patients. Ticagrelor is an anti-platelet drug that widely applied in coronary artery disease. In addition, ticagrelor can increase the level of adenosine. Recent study had indicated that ticagrelor can protect renal function in sepsis induced AKI. However, the detailed mechanism was still unknown. Accordingly, we designed this trial to investigate if the ticagrelor alleviated sepsis induced AKI and demonstrated the potential mechanism that how ticagrelor works. Method C57BL6J mouse received oral ticagrelor (20mg/kg and 50mg/kg) for 7 days and caecum ligation and puncture (CLP) were performed. Adenosine-receptor antagonist was administered (10mg/kg, intraperitoneal injection) to block the adenosine pathway 2h before CLP. After 24h, serum creatinine was measured. PAS staining was used and TUNEL staining was applied to determine the pathological changes and cell apoptosis. Plasma concentrations of TNF-α and IL-1β were detected. Kidney tissue level of TNF-α and IL-1β were determined via qRT-PCR. Western blot was used to determine the expression of signal molecular in kidney. Results In ticagrelor group, PAS staining (fig. 1) showed that less swelling of renal tubules and TUNEL staining (fig. 2) showed the less cell apoptosis compared to CLP. Serum creatinine was significantly lower in ticagrelor group. Plasma TNF-α and IL-1β and kidney expression of TNF-α and IL-1β were significantly lower in ticagrelor group. Adenosine-receptor antagonist significantly blocked the effect of ticagrelor (fig. 3 ang 4). Western blot showed that ticagrelor activate the phosphorylation of AKT and mTOR in kidney. Adenosine-receptor antagonist inhibited the activation of AKT and mTOR (fig. 5). Conclusion The protective effect of ticagrelor was dependent on adenosine-receptor activation with downstream upregulation of phosphorylation of AKT and mTOR in sepsis induced AKI.

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USP10 alleviates sepsis-induced acute kidney injury by regulating Sirt6-mediated Nrf2/ARE signaling pathway

Journal of Inflammation ◽

10.1186/s12950-021-00291-7 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Fei Gao ◽

Mingjiang Qian ◽

Guoyue Liu ◽

Wanping Ao ◽

Dahua Dai ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Epithelial Cell ◽

Western Blot ◽

Cell Apoptosis ◽

Cell Injury ◽

Kidney Injury ◽

Tubular Epithelial Cell ◽

Renal Tubular Epithelial Cell ◽

Renal Tubular

Abstract Background Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. H2O2, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis. Results In this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury. Conclusions This study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.

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