scholarly journals 4-Hydroxychalcone Attenuates Hyperaldosteronism, Inflammation, and Renal Injury in Cryptochrome-Null Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Qi Qu ◽  
Bingguang Dai ◽  
Bo Yang ◽  
Xuelian Li ◽  
Yimin Liu ◽  
...  
Keyword(s):  
Resistant Hypertension ◽  
Renal Injury ◽  
Systolic Pressure ◽  
Kidney Injury ◽  
High Plasma ◽  
Salt Treatment ◽  
Injury Treatment ◽  
The Impact ◽  
Preventive Effects ◽  
Light Chain Enhancer

In the present study, we aimed to investigate the preventive effects of 4-hydroxychalcone (4HCH) on resistant hypertension. We used cryptochrome-null mice, which characteristically show high plasma aldosterone levels, inflammation, and renal injury. The cryptochrome-null mice received high-salt treatment and were treated orally with 4HCH 10 mg/kg, 4HCH 20 mg/kg, and 4HCH 40 mg/kg, respectively. The salt administration in cryptochrome-null mice is able to induce an increase in systolic pressure which is associated with hyperaldosteronism, inflammation, and kidney injury. Treatment with 40 mg/kg 4HCH reduced systolic hypertension, serum IL-1β, and TNF-αlevels and suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and renal injury. The impact of 4HCH on the hyperaldosteronism, inflammation, and kidney injury provides new insights for future development of therapeutic strategies in resistant hypertension.

scholarly journals Autophagy Function and Regulation in Kidney Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 100 ◽  
Author(s):  
Gur P. Kaushal ◽  
Kiran Chandrashekar ◽  
Luis A. Juncos ◽  
Sudhir V. Shah
Keyword(s):  
Cell Death ◽  
Renal Injury ◽  
Mammalian Target Of Rapamycin ◽  
Kidney Injury ◽  
Therapeutic Approaches ◽  
Regulated Necrosis ◽  
Atg Genes ◽  
Cellular Components ◽  
The Impact

Autophagy is a dynamic process by which intracellular damaged macromolecules and organelles are degraded and recycled for the synthesis of new cellular components. Basal autophagy in the kidney acts as a quality control system and is vital for cellular metabolic and organelle homeostasis. Under pathological conditions, autophagy facilitates cellular adaptation; however, activation of autophagy in response to renal injury may be insufficient to provide protection, especially under dysregulated conditions. Kidney-specific deletion of Atg genes in mice has consistently demonstrated worsened acute kidney injury (AKI) outcomes supporting the notion of a pro-survival role of autophagy. Recent studies have also begun to unfold the role of autophagy in progressive renal disease and subsequent fibrosis. Autophagy also influences tubular cell death in renal injury. In this review, we reported the current understanding of autophagy regulation and its role in the pathogenesis of renal injury. In particular, the classic mammalian target of rapamycin (mTOR)-dependent signaling pathway and other mTOR-independent alternative signaling pathways of autophagy regulation were described. Finally, we summarized the impact of autophagy activation on different forms of cell death, including apoptosis and regulated necrosis, associated with the pathophysiology of renal injury. Understanding the regulatory mechanisms of autophagy would identify important targets for therapeutic approaches.

scholarly journals Greater T Regulatory Cells in Females Attenuate DOCA-Salt–Induced Increases in Blood Pressure Versus Males

Hypertension ◽  
2020 ◽  
Vol 75 (6) ◽  
pp. 1615-1623 ◽  
Author(s):  
Kasey M. Belanger ◽  
G. Ryan Crislip ◽  
Ellen E. Gillis ◽  
Mahmoud Abdelbary ◽  
Jacqueline B. Musall ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
T Regulatory Cells ◽  
Critical Role ◽  
Kidney Injury ◽  
Male Rats ◽  
Regulatory Cells ◽  
Salt Treatment ◽  
Males And Females ◽  
The Impact

Hypertension is the most common risk factor for cardiovascular disease, causing over 18 million deaths a year. Although the mechanisms controlling blood pressure (BP) in either sex remain largely unknown, T cells play a critical role in the development of hypertension. Further evidence supports a role for the immune system in contributing to sex differences in hypertension. The goal of the current study was to first, determine the impact of sex on the renal T-cell profiles in DOCA-salt hypertensive males and females and second, test the hypothesis that greater numbers of T regulatory cells (Tregs) in females protect against DOCA-salt–induced increases in BP and kidney injury. Male rats displayed greater increases in BP than females following 3 weeks of DOCA-salt treatment, although increases in renal injury were comparable between the sexes. DOCA-salt treatment resulted in an increase in proinflammatory T cells in both sexes; however, females had more anti-inflammatory Tregs than males. Additional male and female DOCA-salt rats were treated with anti-CD25 to decrease Tregs. Decreasing Tregs significantly increased BP only in females, thereby abolishing the sex difference in the BP response to DOCA-salt. This data supports the hypothesis that Tregs protect against the development of hypertension and are particularly important for the control of BP in females.

Low-dose carvedilol protects against acute septic renal injury in rats during the early and late phases

2015 ◽  
Vol 93 (6) ◽  
pp. 443-450 ◽  
Author(s):  
Hala Salah Abdel kawy
Keyword(s):  
Renal Injury ◽  
Cecal Ligation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Serum Levels ◽  
Renal Perfusion ◽  
Protein Carbonyls ◽  
Necrosis Factor Alpha ◽  
Inflammatory Parameters ◽  
The Impact

Recent findings from septic acute renal injury studies have implicated the mitochondrion as an important factor in kidney injury, and that increased sympathetic nerve activity may contribute to the induction of organ failure. This study investigated the impact of a nondepressor dose of carvedilol, which is a beta-adrenoreceptor antagonist with antioxidant activity, on septic renal injury induced in rats with cecal ligation and puncture (CLP). Three groups of rats were studied. The first group was the sham-operated control. The other 2 groups of rats underwent CLP, and were administered either the vehicle or carvedilol (2.0 mg/kg body mass, by intraperitoneal (i.p.) injection, daily for 2 days as well as 30 min prior to CLP). Kidney function, inflammatory parameters, mitochondrial function, and renal perfusion pressure (RPP) were investigated at 6 and 18 h after CLP. Carvedilol did not significantly induce hypotension, and it significantly improved RPP and renal dysfunction induced with CLP, together with significant reductions in serum levels of interleukin 6 and tumor necrosis factor-alpha. Septic kidney injury mediated increased levels of malondialdehyde and protein carbonyls. Carvedilol also attenuated the decrease in kidney mitochondrial glutathione and nicotinamide adenine dinucleotide phosphate dehydrogenase. Further, intracellular renal edema and inflammation induced with CLP were reduced with carvedilol. These findings suggest renoprotective effects of carvedilol in sepsis.

scholarly journals AT1 and AT2 receptors modulate renal tubular cell necroptosis in angiotensin II-infused renal injury mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Jie Lv ◽  
Haiqin Liang ◽  
Yanping Zheng ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Critical Role ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Renal Tubular Cell ◽  
Ang Ii ◽  
Renal Tubular

AbstractAbnormal renin-angiotensin system (RAS) activation plays a critical role in the initiation and progression of chronic kidney disease (CKD) by directly mediating renal tubular cell apoptosis. Our previous study showed that necroptosis may play a more important role than apoptosis in mediating renal tubular cell loss in chronic renal injury rats, but the mechanism involved remains unknown. Here, we investigate whether blocking the angiotensin II type 1 receptor (AT1R) and/or angiotensin II type 2 receptor (AT2R) beneficially alleviates renal tubular cell necroptosis and chronic kidney injury. In an angiotensin II (Ang II)-induced renal injury mouse model, we found that blocking AT1R and AT2R effectively mitigates Ang II-induced increases in necroptotic tubular epithelial cell percentages, necroptosis-related RIP3 and MLKL protein expression, serum creatinine and blood urea nitrogen levels, and tubular damage scores. Furthermore, inhibition of AT1R and AT2R diminishes Ang II-induced necroptosis in HK-2 cells and the AT2 agonist CGP42112A increases the percentage of necroptotic HK-2 cells. In addition, the current study also demonstrates that Losartan and PD123319 effectively mitigated the Ang II-induced increases in Fas and FasL signaling molecule expression. Importantly, disruption of FasL significantly suppressed Ang II-induced increases in necroptotic HK-2 cell percentages, and necroptosis-related proteins. These results suggest that Fas and FasL, as subsequent signaling molecules of AT1R and AT2R, might involve in Ang II-induced necroptosis. Taken together, our results suggest that Ang II-induced necroptosis of renal tubular cell might be involved both AT1R and AT2R and the subsequent expression of Fas, FasL signaling. Thus, AT1R and AT2R might function as critical mediators.

Effect of alkali therapy with NaHCO3 or THAM on cardiac contractility

1996 ◽  
Vol 270 (5) ◽  
pp. R955-R962
Author(s):  
C. D. Mazer ◽  
B. Naser ◽  
K. S. Kamel
Keyword(s):  
Myocardial Ischemia ◽  
Contractile Function ◽  
Venous Blood ◽  
Systolic Pressure ◽  
Ischemic Myocardium ◽  
Stroke Work ◽  
Length Relationship ◽  
Alkali Therapy ◽  
Myocardial Contractile ◽  
The Impact

We examined the impact of alkali therapy on myocardial contractility in a model of myocardial ischemia in dogs using direct measurements of myocardial contractile function. Myocardial ischemia in the left anterior descending (LAD) artery territory was induced using a perfusion circuit from the internal carotid artery to the LAD artery. Myocardial contractile function was assessed using sonomicrometry for measurement of percent systolic shortening (%SS), preload recruitable stroke work (PRSW) slope, and end-systolic pressure-length relationship (ESPLR) area. Because the blood flow in LAD artery was diminished by approximately 70%, there was a significant decrease in O2 delivery and uptake by the ischemic myocardium. Ischemia led to a significant fall in LAD regional contractile function with %SS decreasing from 15 +/- 2 to 7 +/- 2%, PRSW slope from 82 +/- 10 to 37 +/- 5 mmHg, and ESPLR area from 121 +/- 2 to 48 +/- 14 mmHg.mm (P < 0.05). In six dogs, the intracoronary administration of NaHCO(3) resulted in a significant increase in pH in LAD arterial and venous blood. There was, however, no significant increase in %SS (6 +/- 2), PRSW slope (43 +/- 10 mmHg), or ESPLR area (60 +/- 13 mmHg.mm). Since administration of NaHCO(3) resulted in a significant increase in PCO2 in LAD arterial and venous blood, similar experiments were carried out in five dogs, but with the intracoronary infusion of the amine buffer THAM [tris(hydroxymethyl)aminomethane (Tris) buffer; 2-amino-2-hydroxyl-1,3-propandiol] instead of NaHCO3. Although administration of THAM resulted in a significant increase in pH and a significant decrease in PCO2, in both LAD arterial and venous blood, there was no significant improvement in any of the parameters used to assess myocardial contractile function. In conclusion, administration of alkali (NaHCO3 or THAM) does not enhance the contractile function of the ischemic myocardium.

scholarly journals European registry of type A aortic dissection (ERTAAD) - rationale, design and definition criteria

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fausto Biancari ◽  
Giovanni Mariscalco ◽  
Hakeem Yusuff ◽  
Geoffrey Tsang ◽  
Suvitesh Luthra ◽  
...  
Keyword(s):  
Adverse Events ◽  
Aortic Dissection ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Type A ◽  
Salvage Procedure ◽  
Type A Aortic Dissection ◽  
Mortality And Morbidity ◽  
Link Type ◽  
The Impact

Abstract Background Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient’s conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. Methods Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient’s comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. Discussion The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD. Trial registration ClinicalTrials.gov Identifier: NCT04831073.

scholarly journals SARS-CoV-2 Renal Impairment in Critical Care: An Observational Study of 42 Cases (Kidney COVID)

2021 ◽  
Vol 10 (8) ◽  
pp. 1571
Author(s):  
Antoine-Marie Molina Barragan ◽  
Emmanuel Pardo ◽  
Pierre Galichon ◽  
Nicolas Hantala ◽  
Anne-Charlotte Gianinazzi ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Renal Injury ◽  
Kidney Injury ◽  
Critical Factor ◽  
University Hospital ◽  
Co2 Partial Pressure ◽  
Icu Admission ◽  
Icu Stay ◽  
Arterial Blood ◽  
Mixed Pattern

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to 5% to 16% hospitalization in intensive care units (ICU) and is associated with 23% to 75% of kidney impairments, including acute kidney injury (AKI). The current work aims to precisely characterize the renal impairment associated to SARS-CoV-2 in ICU patients. Forty-two patients consecutively admitted to the ICU of a French university hospital who tested positive for SARS-CoV-2 between 25 March 2020, and 29 April 2020, were included and classified in categories according to their renal function. Complete renal profiles and evolution during ICU stay were fully characterized in 34 patients. Univariate analyses were performed to determine risk factors associated with AKI. In a second step, we conducted a logistic regression model with inverse probability of treatment weighting (IPTW) analyses to assess major comorbidities as predictors of AKI. Thirty-two patients (94.1%) met diagnostic criteria for intrinsic renal injury with a mixed pattern of tubular and glomerular injuries within the first week of ICU admission, which lasted upon discharge. During their ICU stay, 24 patients (57.1%) presented AKI which was associated with increased mortality (p = 0.007), hemodynamic failure (p = 0.022), and more altered clearance at hospital discharge (p = 0.001). AKI occurrence was associated with lower pH (p = 0.024), higher PaCO2 (CO2 partial pressure in the arterial blood) (p = 0.027), PEEP (positive end-expiratory pressure) (p = 0.027), procalcitonin (p = 0.015), and CRP (C-reactive protein) (p = 0.045) on ICU admission. AKI was found to be independently associated with chronic kidney disease (adjusted OR (odd ratio) 5.97 (2.1–19.69), p = 0.00149). Critical SARS-CoV-2 infection is associated with persistent intrinsic renal injury and AKI, which is a risk factor of mortality. Mechanical ventilation settings seem to be a critical factor of kidney impairment.

scholarly journals 87. Utilization of Methicillin-Sensitive/Resistant Staphylococcus aureus Nares Screen to Decrease Vancomycin and Linezolid Use in Hospitalized Patients with Respiratory Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S60-S60
Author(s):  
Noor F Zaidan ◽  
Rachel S Britt ◽  
David Reynoso ◽  
R Scott Ferren
Keyword(s):  
Staphylococcus Aureus ◽  
Respiratory Infections ◽  
Intervention Group ◽  
Kidney Injury ◽  
Post Intervention ◽  
Gram Positive ◽  
Stewardship Program ◽  
Screening Protocol ◽  
The Impact ◽  
Post Intervention Group

Abstract Background Pharmacist-driven protocols for utilization of methicillin-resistant Staphylococcus aureus (MRSA) nares screenings have shown to decrease duration of empiric gram-positive therapy and rates of acute kidney injury (AKI) in patients with respiratory infections. This study evaluated the impact of a pharmacist-driven MRSA nares screening protocol on duration of vancomycin or linezolid therapy (DT) in respiratory infections. Methods Patients aged 18 years and older with a medication order of vancomycin or linezolid for respiratory indication(s) were included. The MRSA nares screening protocol went into effect in October 2019. The protocol allowed pharmacists to order an MRSA nares polymerase chain reaction (PCR) for included patients, while the Antimicrobial Stewardship Program (ASP) made therapeutic recommendations for de-escalation of empiric gram-positive coverage based on negative MRSA nares screenings, if clinically appropriate. Data for the pre-intervention group was collected retrospectively for the months of October 2018 to March 2019. The post-intervention group data was collected prospectively for the months of October 2019 to March 2020. Results Ninety-seven patients were evaluated within both the pre-intervention group (n = 50) and post-intervention group (n = 57). Outcomes for DT (38.2 hours vs. 30.9 hours, P = 0.601) and AKI (20% vs. 14%, P = 0.4105) were not different before and after protocol implementation. A subgroup analysis revealed a significant reduction in DT within the pre- and post-MRSA PCR groups (38.2 hours vs. 24.8 hours, P = 0.0065) when pharmacist recommendations for de-escalation were accepted. Conclusion A pharmacist-driven MRSA nares screening protocol did not affect the duration of gram-positive therapy for respiratory indications. However, there was a reduction in DT when pharmacist-driven recommendations were accepted. Disclosures All Authors: No reported disclosures

scholarly journals Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 572
Author(s):  
Jung-Yeon Kim ◽  
Jungmin Jo ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Renal Injury ◽  
Manganese Superoxide Dismutase ◽  
Immune Cell ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Pleiotropic Effects ◽  
Induced Apoptosis ◽  
Vascular Adhesion

Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.

scholarly journals Does deeper hypothermia reduce the risk of acute kidney injury after circulatory arrest for aortic arch surgery?

2021 ◽  
Author(s):  
Andrew M Vekstein ◽  
Babtunde A Yerokun ◽  
Oliver K Jawitz ◽  
Julie W Doberne ◽  
Jatin Anand ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Circulatory Arrest ◽  
Aortic Surgery ◽  
Multivariable Analysis ◽  
Kidney Injury ◽  
Deep Hypothermia ◽  
Moderate Hypothermia ◽  
Bladder Temperature ◽  
Increased Risk ◽  
The Impact

Abstract OBJECTIVES The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS A total of 85% (n = 645) of patients underwent deep hypothermia (14.1–20.0°C), 11% (n = 83) low-moderate hypothermia (20.1–24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1–28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1–34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P &gt; 0.05). CONCLUSIONS In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.

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