scholarly journals Intravenous Arginine Administration Downregulates NLRP3 Inflammasome Activity and Attenuates Acute Kidney Injury in Mice with Polymicrobial Sepsis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Sharon Angela Tanuseputero ◽  
Ming-Tsan Lin ◽  
Sung-Ling Yeh ◽  
Chiu-Li Yeh
Keyword(s):  
Acute Kidney Injury ◽  
Protein Expression ◽  
Kidney Function ◽  
Nlrp3 Inflammasome ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Major Complication ◽  
Receptor Protein ◽  
No Production ◽  
Inflammasome Activity

Acute kidney injury (AKI) is a major complication of sepsis. Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes are multiprotein complexes that mediate septic AKI. L-arginine (Arg) is a conditionally essential amino acid in catabolic conditions and a substrate for nitric oxide (NO) production; however, its use in sepsis is controversial. This study investigated the effect of intravenous Arg supplementation on modulating NLRP3 inflammasome activity in relation to septic AKI. Mice were divided into normal control (NC), sham, sepsis saline (SS), and sepsis Arg (SA) groups. In order to investigate the role of NO, L-N6-(1-iminoethyl)-lysine hydrochloride (L-NIL), an inducible NO synthase inhibitor, was administered to the sepsis groups. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg via tail vein 1 h after CLP. Mice were sacrificed at 6, 12, and 24 h after sepsis. The results showed that compared to the NC group, septic mice had higher plasma kidney function parameters and lower Arg levels. Also, renal NLRP3 inflammasome protein expression and tubular injury score increased. After Arg treatment, plasma Arg and NO levels increased, kidney function improved, and expressions of renal NLRP3 inflammasome-related proteins were downregulated. Changes in plasma NO and renal NLRP3 inflammasome-related protein expression were abrogated when L-NIL was given to the Arg sepsis groups. Arg plus L-NIL administration also attenuated kidney injury after CLP. The findings suggest that intravenous Arg supplementation immediately after sepsis restores plasma Arg levels and is beneficial for attenuating septic AKI, partly via NO-mediated NLRP3 inflammasome inhibition.

scholarly journals Sepsis-induced acute kidney injury: kidney protection effects by antioxidants

2018 ◽  
Vol 71 (4) ◽  
pp. 1921-1927 ◽  
Author(s):  
Carolina Ferreira Vasco ◽  
Mirian Watanabe ◽  
Cassiane Dezoti da Fonseca ◽  
Maria de Fátima Fernandes Vattimo
Keyword(s):  
Blood Pressure ◽  
Acute Kidney Injury ◽  
Creatinine Clearance ◽  
Experimental Model ◽  
Kidney Function ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Cecal Ligation And Puncture ◽  
Antioxidant Action ◽  
Average Blood Pressure

ABSTRACT Objective: To evaluate the antioxidant action of N-acetylcysteine and diosmin-hesperidin in an experimental model of sepsis-induced acute kidney injury in rats. Methods: The study used 20 Wistar adult male rats divided into the following groups: control (laparotomy with no induction of abdominal sepsis), sepsis (experimental model of sepsis with cecal ligation and puncture), N-acetylcysteine + sepsis and diosmin-hesperidin + sepsis. The evaluation contemplated physiological parameters (temperature, glycemia, and average blood pressure), kidney function (creatinine clearance), oxidative stress (urinary peroxides) and kidney histology. Results: The animals submitted to cecal ligation and puncture (sepsis) presented lower body temperature, lower average blood pressure, reduced creatinine clearance and increased urinary hydrogen peroxide levels. Treatment with diosmin-hesperidin improved kidney function and led to a reduction in the excretion of oxidative metabolites. Conclusion: The present study highlighted the protective antioxidant action of diosmin-hesperidin in the experimental model of sepsis-induced acute kidney injury.

scholarly journals Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury

2021 ◽  
Vol 22 (3) ◽  
pp. 1382
Author(s):  
Jelena Nesovic Ostojic ◽  
Milan Ivanov ◽  
Nevena Mihailovic-Stanojevic ◽  
Danijela Karanovic ◽  
Sanjin Kovacevic ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protein Expression ◽  
Hyperbaric Oxygen ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

scholarly journals Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yue Zhang ◽  
Hongdong Huang ◽  
Wenhu Liu ◽  
Sha Liu ◽  
Xue Yan Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Endothelial Glycocalyx ◽  
Endothelial Progenitor ◽  
Marker Proteins ◽  
Related Transcription Factor

AbstractThe role of microRNA-21-5p (miR-21-5p) in sepsis-induced acute kidney injury (AKI) has been seldom discussed. Therefore, the objective of this present study was to investigate the mechanism of endothelial progenitor cells-derived exosomes (EPCs-exos) in sepsis-induced AKI via miR-21-5p/runt-related transcription factor 1 (RUNX1) axis. miR-21-5p was downregulated and RUNX1 was upregulated in the kidney of cecal ligation and puncture (CLP) rats, and miR-21-5p targeted RUNX1. Elevation of miR-21-5p improved renal function and renal tissue pathological damage, attenuated serum inflammatory response, as well as reduced apoptosis and oxidative stress response in renal tissues, and regulated endothelial glycocalyx damage marker proteins syndecan-1 and heparanase-1 in CLP rats. Overexpression of RUNX1 abolished the impacts of elevated miR-21-5p in CLP rats. Also, EPCs-exos upregulated miR-21-5p expression, and functioned similar to elevation of miR-21-5p for CLP rats. Downregulating miR-21-5p partially reversed the effects of EPCs-exos on sepsis-induced AKI. Collectively, our study suggests that EPCs release miR-21-5p-containing exosomes to alleviate sepsis-induced AKI through RUNX1 silencing.

scholarly journals Assessment of Kidney Function After Transcatheter Aortic Valve Replacement

2021 ◽  
Vol 8 ◽  
pp. 205435812110180
Author(s):  
Orit Kliuk-Ben Bassat ◽  
Sapir Sadon ◽  
Svetlana Sirota ◽  
Arie Steinvil ◽  
Maayan Konigstein ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Function ◽  
Transcatheter Aortic Valve Replacement ◽  
Kidney Injury ◽  
Single Center ◽  
Transcatheter Aortic Valve ◽  
Single Center Study ◽  
Center Study

Background: Transcatheter aortic valve replacement (TAVR), although associated with an increased risk for acute kidney injury (AKI), may also result in improvement in renal function. Objective: The aim of this study is to evaluate the magnitude of kidney function improvement (KFI) after TAVR and to assess its significance on long-term mortality. Design: This is a prospective single center study. Setting: The study was conducted in cardiology department, interventional unit, in a tertiary hospital. Patients: The cohort included 1321 patients who underwent TAVR. Measurements: Serum creatinine level was measured at baseline, before the procedure, and over the next 7 days or until discharge. Methods: Kidney function improvement was defined as the mirror image of AKI, a reduction in pre-procedural to post-procedural minimal creatinine of more than 0.3 mg/dL, or a ratio of post-procedural minimal creatinine to pre-procedural creatinine of less than 0.66, up to 7 days after the procedure. Patients were categorized and compared for clinical endpoints according to post-procedural renal function change into 3 groups: KFI, AKI, or preserved kidney function (PKF). The primary endpoint was long-term all-cause mortality. Results: The incidence of KFI was 5%. In 55 out of 66 patients patients, the improvement in kidney function was minor and of unclear clinical significance. Acute kidney injury occurred in 19.1%. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 was a predictor of KFI after multivariable analysis (odds ratio = 0.93 to develop KFI; confidence interval [95% CI]: 0.91-0.95, P < .001). Patients in the KFI group had a higher Society of Thoracic Surgery (STS) score than other groups. Mortality rate did not differ between KFI group and PKF group (43.9% in KFI group and 33.8% in PKF group) but was significantly higher in the AKI group (60.7%, P < .001). Limitations: The following are the limitations: heterozygous definitions of KFI within different studies and a single center study. Although data were collected prospectively, analysis plan was defined after data collection. Conclusions: Improvement in kidney function following TAVR was not a common phenomenon in our cohort and did not reduce overall mortality rate.

scholarly journals Acute kidney injury and its outcomes in melioidosis

2021 ◽  
Author(s):  
Ravindra Attur Prabhu ◽  
Tushar Shaw ◽  
Indu Ramachandra Rao ◽  
Vandana Kalwaje Eshwara ◽  
Shankar Prasad Nagaraju ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Function ◽  
Univariate Analysis ◽  
Kidney Injury ◽  
Function Recovery ◽  
Kidney Involvement ◽  
Duration Of Hospitalization ◽  
Observational Cohort ◽  
Stage 1 ◽  
Urinary Abnormalities

Abstract Background Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described. Aim This study aimed to assess the risk of acute kidney injury (AKI) and its outcomes in melioidosis. Methods A retrospective observational cohort study was performed. Case records of consecutive patients with culture-confirmed melioidosis, observed from January 1st, 2012 through December 31st, 2019 were analysed for demographics, presence of comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), and presence of bacteraemia, sepsis, shock, AKI, and urinary abnormalities. The outcomes we studied were: mortality, need for hospitalisation in an intensive care unit (ICU), duration of hospitalization. We then compared the outcomes between patients with and without AKI. Results Of 164 patients, AKI was observed in 59 (35.98%), and haemodialysis was required in eight (13.56%). In the univariate analysis, AKI was associated with CKD (OR 5.83; CI 1.140–29.90, P = 0.03), bacteraemia (OR 8.82; CI 3.67–21.22, P < 0.001) and shock (OR 3.75; CI 1.63–8.65, P = 0.04). In the multivariate analysis, CKD (adjusted OR 10.68; 95% CI 1.66–68.77; P = 0.013) and bacteraemia (adjusted OR 8.22; 95% CI 3.15–21.47, P < 0.001) predicted AKI. AKI was associated with a greater need for ICU care (37.3% vs. 13.3%, P = 0.001), and mortality (32.2% vs. 5.7%, P < 0.001). Mortality increased with increasing AKI stage, i.e. stage 1 (OR 3.52, CI 0.9–13.7, P = 0.07), stage 2 (OR 6.79, CI 1.92–24, P = 0.002) and stage 3 (OR 17.8, CI 5.05–62.8, P < 0.001), however kidney function recovered in survivors. Hyponatremia was observed in 138 patients (84.15%) and isolated urinary abnormalities were seen in 31(18.9%). Conclusions AKI is frequent in melioidosis and occurred in 35.9% of our cases. Hyponatremia is likewise common. AKI was predicted by bacteraemia and CKD, and was associated with higher mortality and need for ICU care; however kidney function recovery was observed in survivors. Graphic abstract

α2-Adrenoceptor agonist dexmedetomidine protects septic acute kidney injury through increasing BMP-7 and inhibiting HDAC2 and HDAC5

2012 ◽  
Vol 303 (10) ◽  
pp. F1443-F1453 ◽  
Author(s):  
Chung-Hsi Hsing ◽  
Chiou-Feng Lin ◽  
Edmund So ◽  
Ding-Ping Sun ◽  
Tai-Chi Chen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Histone H3 ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Protective Effects ◽  
Tnf Α

Bone morphogenetic protein (BMP)-7 protects sepsis-induced acute kidney injury (AKI). Dexmedetomidine (DEX), an α2-adrenoceptor (α2-AR) agonist, has anti-inflammatory effects. We investigated the protective effects of DEX on sepsis-induced AKI and the expression of BMP-7 and histone deacetylases (HDACs). In vitro , the effects of DEX or trichostatin A (TSA, an HDAC inhibitor) on TNF-α, monocyte chemotactic protein (MCP-1), BMP-7, and HDAC mRNA expression in LPS-stimulated rat renal tubular epithelial NRK52E cells, was determined using real-time PCR. In vivo, mice were intraperitoneally injected with DEX (25 μg/kg) or saline immediately and 12 h after cecal ligation and puncture (CLP) surgery. Twenty-four hours after CLP, we examined kidney injury and renal TNF-α, MCP-1, BMP-7, and HDAC expression. Survival was monitored for 120 h. LPS increased HDAC2, HDAC5, TNF-α, and MCP-1 expression, but decreased BMP-7 expression in NRK52E cells. DEX treatment decreased the HDAC2, HDAC5, TNF-α, and MCP-1 expression, but increased BMP-7 and acetyl histone H3 expression, whose effects were blocked by yohimbine, an α2-AR antagonist. With DEX treatment, the LPS-induced TNF-α expression and cell death were attenuated in scRNAi-NRK52E but not BMP-7 RNAi-NRK52E cells. In CLP mice, DEX treatment increased survival and attenuated AKI. The expression of HDAC2, HDAC5, TNF-α, and MCP-1 mRNA in the kidneys of CLP mice was increased, but BMP-7 was decreased. However, DEX treatment reduced those changes. DEX reduces sepsis-induced AKI by decreasing TNF-α and MCP-1 and increasing BMP-7, which is associated with decreasing HDAC2 and HDAC5, as well as increasing acetyl histone H3.

MO388DEVELOPMENT OF ACUTE KIDNEY INJURY DURING A RHABDOMYOLYSIS EPISODE: DIFFERENCES IN LONG-TERM KIDNEY FUNCTION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sara Núñez Delgado ◽  
Miren Iriarte-Abril ◽  
Júlia Farrera-Núñez ◽  
Sergi Pascual-Sánchez ◽  
Laia Sans-Atxer ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Function ◽  
Kidney Injury ◽  
Inpatient Mortality ◽  
Short Term ◽  
Worse Prognosis

Abstract Background and Aims Acute renal failure (AKI) associated to rhabdomyolysis conditions a worse prognosis in short-term, its implication in the long-term renal function has been less evaluated. Method Retrospective analysis of patients diagnosed with rhabdomyolysis defined by creatinine kinase &gt; 5000 IU/L between 2015-2019. Basal and 12-month renal function was evaluated. AKI was classified as either non-severe (AKI-KDIGO 1/2) or severe (AKI-KDIGO 3). Results Eighty-seven patients were included, 25 (28.74%) had some degree of chronic kidney disease (CKD) on admission. 56 (64.37%) had AKI on admission, 17 of which were severe (6 required hemodialysis). The patients with AKI had more cardiovascular disease (CVD) and worse analytical parameters on admission (table). Patients with severe AKI showed no difference in CVD from those with non-severe AKI but were younger and had more hyperkalemia. There were no significant differences between patients with severe AKI who required hemodialysis and those who did not. Inpatient mortality was 8%, higher in patients with AKI but without differences according to severity. In 45 patients kidney function was available 12 months after the episode, loss of eGF was -4.90 ± 14.35 ml/min-1.73m2 (p=0.007). There was no difference between patients who developed AKI and those who did not (-4.10 ± 14.4 vs. -5.39 ± 14.57 ml/min-1.73m2; p=0.67), nor between non-severe and severe AKI (-5.50 ± 14.76 vs. -5.12 ± 15.08ml/min-1.73m2; p=0.98). Of the 33 patients without previous CKD, 5 developed CKD, with greater decrease in eGF than those who did not (-22.69 ± 6.04 vs. -2.63 ± 13.92 ml/min-1.73m2; p=0.003). Female sex (60% vs. 12%; p=0.031) and previous basal eGF (72.22 ± 4.37 vs. 95.6±19.97 ml/min-1.72m2; p=0.016) were related to this deterioration. Conclusion After an episode of rhabdomyolysis, the loss of eGF is similar in patients who develop AKI compared to those who do not.

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