Haemodynamic and renal effects of clonidine in an ovine model of severe sepsis and septic acute kidney injury

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).

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An Ovine Model for Studying the Pathophysiology of Septic Acute Kidney Injury

Methods in Molecular Biology - Traumatic and Ischemic Injury ◽

10.1007/978-1-4939-7526-6_16 ◽

2018 ◽

pp. 207-218 ◽

Cited By ~ 8

Author(s):

Yugeesh R. Lankadeva ◽

Junko Kosaka ◽

Roger G. Evans ◽

Clive N. May

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Ovine Model ◽

Septic Acute Kidney Injury

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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

Blood Purification ◽

10.1159/000499633 ◽

2019 ◽

Vol 47 (Suppl. 3) ◽

pp. 59-64 ◽

Cited By ~ 3

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.

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Acute kidney injury in severe sepsis

10.1093/med/9780199592548.003.0244_update_001 ◽

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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Effect of Probiotics and Prebiotics in Renal Function in Septic Acute Kidney Injury Patients

Case Medical Research ◽

10.31525/ct1-nct03877081 ◽

2019 ◽

Author(s):

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Kidney Injury ◽

Septic Acute Kidney Injury

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

Cell Death and Disease ◽

10.1038/s41419-021-03865-8 ◽

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.

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