scholarly journals Augmented Adsorptive Blood Purification during Continuous Veno-Venous Haemodiafiltration in a Severe Septic, Acute Kidney Injury Patient: Use of oXiris®: A Single Centre Case Report

2019 ◽  
Vol 47 (Suppl. 3) ◽  
pp. 59-64 ◽  
Author(s):  
Han Khim Tan ◽  
Manish Kaushik ◽  
Chee Wooi Tan ◽  
Zhong Hong Liew ◽  
Su Hooi Teo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Severe Sepsis ◽  
Kidney Injury ◽  
Critically Ill Patient ◽  
High Dose ◽  
Septic Acute Kidney Injury ◽  
Injury Patient ◽  
Patient Use ◽  
Adsorptive Properties

The use of the oXiris® haemofilter during continuous veno-venous haemodiafiltration (CVVHDF) for acute kidney injury (AKI) and severe sepsis is not completely understood. Although this filter has in vitro adsorptive properties for blood-borne cytokines and other humoural mediators of sepsis, its clinical usefulness is uncertain. Given its inherent adsorptive limitation for septic mediators, we developed a CVVHDF protocol in which the oXiris haemofilter was electively changed every 12 h even though there was no clotting or adverse circuit pressures. Augmented filter membrane adsorption was conducted for 3 consecutive days. We treated a critically ill patient with severe sepsis secondary to a gram-negative bacterial infection and sepsis-associated acute kidney injury (SA- AKI) in this way. The patient required high-dose vasopressor support, required mechanical ventilation, had received 12 h of CVVHDF with conventional M100 haemofilter, was on broad spectrum antibiotics and other conventional intensive care unit (ICU) care, prior to institution of the frequent oXiris haemofilter change protocol. Following the start of elective 12 hourly oXiris filter change, the patient showed reduction in the need for vasopressor and by Day 4 of this SA- AKI frequent filter change protocol, vasopressor requirement ceased, he was extubated. He survived ICU and but not hospital stay. To this end, more clinical studies are needed.

scholarly journals RIP3 impedes transcription factor EB to suppress autophagic degradation in septic acute kidney injury

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Ruizhao Li ◽  
Xingchen Zhao ◽  
Shu Zhang ◽  
Wei Dong ◽  
Li Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Nuclear Translocation ◽  
Kidney Injury ◽  
Septic Acute Kidney Injury ◽  
Transcription Factor Eb ◽  
Autophagic Degradation ◽  
Lps Treatment

AbstractAutophagy is an important renal-protective mechanism in septic acute kidney injury (AKI). Receptor interacting protein kinase 3 (RIP3) has been implicated in the renal tubular injury and renal dysfunction during septic AKI. Here we investigated the role and mechanism of RIP3 on autophagy in septic AKI. We showed an activation of RIP3, accompanied by an accumulation of the autophagosome marker LC3II and the autophagic substrate p62, in the kidneys of lipopolysaccharide (LPS)-induced septic AKI mice and LPS-treated cultured renal proximal tubular epithelial cells (PTECs). The lysosome inhibitor did not further increase the levels of LCII or p62 in LPS-treated PTECs. Moreover, inhibition of RIP3 attenuated the aberrant accumulation of LC3II and p62 under LPS treatment in vivo and in vitro. By utilizing mCherry-GFP-LC3 autophagy reporter mice in vivo and PTECs overexpression mRFP-GFP-LC3 in vitro, we observed that inhibition of RIP3 restored the formation of autolysosomes and eliminated the accumulated autophagosomes under LPS treatment. These results indicated that RIP3 impaired autophagic degradation, contributing to the accumulation of autophagosomes. Mechanistically, the nuclear translocation of transcription factor EB (TFEB), a master regulator of the lysosome and autophagy pathway, was inhibited in LPS-induced mice and LPS-treated PTECs. Inhibition of RIP3 restored the nuclear translocation of TFEB in vivo and in vitro. Co-immunoprecipitation further showed an interaction of RIP3 and TFEB in LPS-treated PTECs. Also, the expression of LAMP1 and cathepsin B, two potential target genes of TFEB involved in lysosome function, were decreased under LPS treatment in vivo and in vitro, and this decrease was rescued by inhibiting RIP3. Finally, overexpression of TFEB restored the autophagic degradation in LPS-treated PTECs. Together, the present study has identified a pivotal role of RIP3 in suppressing autophagic degradation through impeding the TFEB-lysosome pathway in septic AKI, providing potential therapeutic targets for the prevention and treatment of septic AKI.

scholarly journals IL-17A activated by Toll-like receptor 9 contributes to the development of septic acute kidney injury

2020 ◽  
Vol 318 (1) ◽  
pp. F238-F247
Author(s):  
Yoshitaka Naito ◽  
Takayuki Tsuji ◽  
Soichiro Nagata ◽  
Naoko Tsuji ◽  
Tomoyuki Fujikura ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Critical Role ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Γδt Cells ◽  
Morphological Aspects ◽  
Septic Acute Kidney Injury

Toll-like receptor 9 (TLR9), which is activated by endogenously released mtDNA during sepsis, contributes to the development of polymicrobial septic acute kidney injury (AKI). However, downstream factors of TLR9 to AKI remain unknown. We hypothesized that IL-17A activated by TLR9 may play a critical role in septic AKI development. To determine the effects of TLR9 on IL-17A production in septic AKI, we used a cecal ligation and puncture (CLP) model in Tlr9 knockout ( Tlr9KO) mice and wild-type (WT) littermates. We also investigated the pathway from TLR9 activation in dendritic cells (DCs) to IL-17A production by γδT cells in vitro. To elucidate the effects of IL-17A on septic AKI, Il-17a knockout ( Il-17aKO) mice and WT littermates were subjected to CLP. We further investigated the relationship between the TLR9-IL-17A axis and septic AKI by intravenously administering recombinant IL-17A or vehicle into Tlr9KO mice and assessing kidney function. IL-17A levels in both plasma and the peritoneal cavity and mRNA levels of IL-23 in the spleen were significantly higher in WT mice after CLP than in Tlr9KO mice. Bone marrow-derived DCs activated by TLR9 induced IL-23 and consequently promoted IL-17A production in γδT cells in vitro. Knockout of Il-17a improved survival, functional and morphological aspects of AKI, and splenic apoptosis after CLP. Exogenous IL-17A administration aggravated CLP-induced AKI attenuated by knockout of Tlr9. TLR9 in DCs mediated IL-17A production in γδT cells during sepsis and contributed to the development of septic AKI.

scholarly journals Haemodynamic effects of clonidine in an ovine model of severe sepsis with septic acute kidney injury

Critical Care ◽  
2014 ◽  
Vol 18 (Suppl 1) ◽  
pp. P414
Author(s):  
P Calzavacca ◽  
Y Lankadeva ◽  
L Booth ◽  
S Bailey ◽  
M Bailey ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Severe Sepsis ◽  
Kidney Injury ◽  
Haemodynamic Effects ◽  
Ovine Model ◽  
Septic Acute Kidney Injury

Association between left ventricular diastolic dysfunction and septic acute kidney injury in severe sepsis and septic shock: A multicenter retrospective study

Perfusion ◽  
2021 ◽  
pp. 026765912198896
Author(s):  
Guangwei Yu ◽  
Kun Cheng ◽  
Qing Liu ◽  
Xiaohong Lin ◽  
Fenghui Lin ◽  
...  
Keyword(s):  
Septic Shock ◽  
Acute Kidney Injury ◽  
Severe Sepsis ◽  
Retrospective Study ◽  
Kidney Injury ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Septic Acute Kidney Injury ◽  
Ventricular Diastolic Dysfunction ◽  
Sepsis And Septic Shock

Introduction: Left ventricular diastolic dysfunction (LVDD) adversely impacts renal function, and E/e′ is a significant predictor of adverse kidney events under different clinical conditions. However, no studies have evaluated the association between LVDD and septic acute kidney injury (AKI) among patients with severe sepsis and septic shock. Methods: This multicenter retrospective study evaluated adult patients with severe sepsis or septic shock between January 1, 2013, and December 31, 2019, who underwent echocardiography within 24 hours after admission to an intensive care unit. Results: A total of 495 adult patients were enrolled in the study. LVDD grades II and III were associated with severe (stage 3) AKI ( p < 0.001, p for trend < 0.001). E/e′ and e′ were risk factors for septic AKI (OR, 1.155; 95% CI, 1.088–1.226, p < 0.001; and OR, 7.218; 95% CI, 2.942–17.712, p < 0.001, respectively) in the multivariate logistic regression analysis. The area under the receiver operating characteristic curve of E/e′ and e′ was 0.728 (95% CI, 0.680–0.777, p < 0.001) and 0.715 (95% CI, 0.665–0.764, p < 0.001), respectively. Conclusions: LVDD was associated with septic AKI, and E/e′ and e′ are useful predictors of septic AKI among patients with severe sepsis or septic shock. Trial registration The study was registered at the Chinese Clinical Trial Registry (Protocol No. ChiCTR2000033083).

scholarly journals Isoliquiritigenin attenuates LPS-induced acute kidney injury through suppression of HMGB1 pathway in renal tubular against ferritinophagy

2020 ◽  
Author(s):  
Yun Tang ◽  
Yanmei Wang ◽  
Chan Wang ◽  
Meidie Yu ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Dysfunction ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Renal Tubular Cells ◽  
Septic Acute Kidney Injury ◽  
Life Threatening ◽  
Renal Tubular

Abstract Septic acute kidney injury (AKI) mainly results in life-threatening renal dysfunction involving renal tubular injury to bring heavy burden to patients in intensive care unit (ICU). However, there is still a lack of therapy to prevent septic AKI effectively and inexpensive. To observe the role and novel mechanism of isoliquiritigenin (ISL) which isolated from the roots of licorice in septic AKI, we used LPS to induce renal tubular injury upon septic AKI both in vitro and in vivo. 50mg/kg ISL and 5 mg/kg Ferrostatin-1 were once given to the male C57BL/6 mice one hour before 1 mg/kg LPS i.p injection. 50 μM and 100 μM ISL respectively pre-treat the human renal tubular cells 5 hrs before 2 μg/ml LPS stimulation. We found ISL pretreatment apparently reversed LPS-induced renal dysfunction and ameliorated murine renal tubular injury by suppression HMGB1 pathway. Furthermore, we observed that LPS induced autophagy and ferroptosis in renal tubular, whereas ISL pretreatment significantly suppress autophagy and ferroptosis of renal tubular both in vitro and in vivo. Mechanically, autophagy activated ferroptosis via NCOA4-mediated ferritinophagy. Moreover, HMGB1 is required for ferritinophagy in renal tubular. ISL treatment inhibited the expression of HMGB1. Taken together, these results suggest that ISL protects LPS-induced acute kidney injury through suppression of HMGB1 pathway in renal tubular against ferritinophagy.

scholarly journals LncRNA-UCA1 Alleviates Septic Acute Kidney Injury through Regulating Endoplasmic Reticulum Stress in LPS-treated HK-2 Cells

2021 ◽  
Author(s):  
TT Yu ◽  
FL Cai ◽  
J Niu
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Noncoding Rna ◽  
Kidney Injury ◽  
Tunel Staining ◽  
Septic Acute Kidney Injury ◽  
Commercial Kits

AbstractObjectiveSeptic acute kidney injury (AKI) is an important cause of death in patients with sepsis. This study sought to explore the function of the long noncoding RNA, urothelial carcinoma associated 1 (lncRNA-UCA1), in septic AKI and determine the underlying molecular mechanism.MethodsHK-2 cells were treated with lipopolysaccharide (LPS) to establish an in vitro model of septic AKI. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of lncRNA-UCA1. CCK-8 assay was used to detect the viability of HK-2 cells. Western blotting was utilized to examine protein expression. The contents of SOD, GSH, MDA, and ROS were determined using commercial kits. The apoptosis rate was calculated using TUNEL staining and flow cytometry.ResultsLncRNA-UCA1 was down-regulated in LPS-treated HK-2 cells. LPS significantly reduced the content of SOD and GSH in HK-2 cells, increased the production of MDA and ROS, and led to an increase in the rate of apoptosis. However, overexpression of lncRNA-UCA1 protected HK-2 cells from oxidative stress and apoptosis. Furthermore, LPS induced endoplasmic reticulum (ER) stress in HK-2 cells, which was inhibited by overexpression of lncRNA-UCA1.ConclusionOverexpression of lncRNA-UCA1 inhibited LPS-induced oxidative stress and apoptosis of HK-2 cells by suppressing ER stress.

Acute kidney injury in severe sepsis

2018 ◽  
Author(s):  
John Prowle ◽  
Rinaldo Bellomo
Keyword(s):  
Acute Kidney Injury ◽  
Severe Sepsis ◽  
Kidney Injury ◽  
Source Control ◽  
Prognostic Information ◽  
Creatinine Concentration ◽  
Septic Acute Kidney Injury ◽  
Increased Risk ◽  
Arteriolar Tone ◽  
Sepsis And Septic Shock

Septic acute kidney injury (S-AKI) accounts for close to 50% of all cases of AKI in ICU and, in its various forms, affects between 15% and 20% of ICU patients. Patients typically present with clinical evidence of severe sepsis and septic shock, developing oliguria or anuria, and rapidly rising serum creatinine concentration. The pathophysiology of S-AKI is poorly understood. Although haemodynamic factors might play a role in the loss of glomerular filtration rate, this may not be through the induction of renal ischaemia. Inflammation, microvascular shunting, and changes in glomerular arteriolar tone may play important roles. Much evidence suggests that clinically urinalysis fails to provide useful diagnostic or prognostic information in this setting but novel biomarkers and urine microscopy may provide more useful prognostic information.The treatment of S-AKI remains based on the treatment of the aetiology of sepsis with source control and appropriate antibiotics, supportive treatment of systemic illness including, in severe cases, renal replacement therapy (RRT). Because most patients with S-AKI requiring RRT are critically ill and haemodynamically unstable, RRT in these patients is best provided as continuous RRT.Approximately 50% of patients with severe S-AKI survive to hospital discharge and, among those who survive, approximately 85–90% recover to dialysis independence. However, those patients who recover appear to be at increased risk of developing chronic kidney disease over the following years.

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