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Cancer Medicine Feb 2023Dirty necrosis (DN) in renal cell carcinoma (RCC) is morphologically characterized by abundant neutrophil infiltration and has significant potential as an unfavorable...
AIM
Dirty necrosis (DN) in renal cell carcinoma (RCC) is morphologically characterized by abundant neutrophil infiltration and has significant potential as an unfavorable prognostic indicator. This study aimed to analyze the pathological and biological features of DN.
MATERIALS AND METHODS
A total of 81 RCC tumors, including 33 cases of DN and 48 cases of tumor necrosis without DN features (ghost necrosis [GN]), were enrolled in this study. We compared the number of neutrophils; the activation of cell death pathways, including ferroptosis, NETosis, and apoptosis; the rate of epithelial-mesenchymal transition (EMT); and proliferation status using immunohistochemistry. We further assessed the effect of the necrosis type on systemic inflammation.
RESULTS
DN tumors had a significantly higher number of neutrophils in both areas around the necrotic foci and far from the necrotic foci. Ferroptosis status did not differ between DN and GN; however, DN tumors had significantly larger areas exhibiting cell detritus with neutrophil extracellular traps (NETs) detected by citrullinated histone H3 (citH3) than GN tumors. DN tumors also had more apoptotic cells within areas around the necrotic foci. There was no significant difference between the EMT and proliferation status between DN and GN groups. Systemic inflammation markers including C-reactive protein (CRP), CRP-to-albumin ratio (CRP/Alb), platelet-to-lymphocyte ratio (PLR), and hemoglobin were significantly higher in patients with DN. In addition, some of these inflammation markers (CRP/Alb and PLR) significantly decreased after surgery.
CONCLUSIONS
DN in RCC is characterized by NETs production and systemic inflammation.
Topics: Humans; Carcinoma, Renal Cell; Inflammation; Neutrophils; C-Reactive Protein; Kidney Neoplasms; Necrosis
PubMed: 36127822
DOI: 10.1002/cam4.5249 -
Acta Physiologica (Oxford, England) Jan 2015One of the frequent clinical complications that results in billions of dollars in healthcare costs annually in the United States is acute kidney injury (AKI). Ischaemia... (Review)
Review
One of the frequent clinical complications that results in billions of dollars in healthcare costs annually in the United States is acute kidney injury (AKI). Ischaemia reperfusion (IR) injury is a major cause AKI. Unfortunately, no effective treatment or preventive measure for AKI exists. With increased surgical complexity coupled with increasing number of elderly, the incidence of AKI is becoming more frequent. Adenosine is a metabolic breakdown product of adenosine triphosphate (ATP) and contributes to the regulation of multiple physiological events. Extracellular adenosine activates four subtypes of adenosine receptors (AR) including A1 AR, A2 A AR, A2 B AR and A3 AR. In the kidney, adenosine regulates glomerular filtration rate, vascular tone, renin release and is an integrative part of tubular glomerular feedback signal to the afferent arterioles. In addition, each AR subtype powerfully modulates renal IR injury. The A1 AR activation protects against ischaemic insult by reducing apoptosis, necrosis and inflammation. Activation of A2 A AR protects against renal injury by modulating leucocyte-mediated inflammation as well as directly reducing renal tubular inflammation. Activation of A2 B AR acts via direct activation of renal parenchymal as well as renovascular receptors and is important in kidney preconditioning. Finally, activation of A3 AR exacerbates renal damage following renal IR injury while A3 AR antagonism attenuates renal damage following ischaemic insult. Latest body of research suggests that kidney AR modulation may be a promising approach to treat ischaemic AKI. This brief review focuses on the signalling pathways of adenosine in the kidney followed by the role for various AR modulations in protecting against ischaemic AKI.
Topics: Animals; Apoptosis; Humans; Kidney Diseases; Necrosis; Receptors, Purinergic P1; Reperfusion Injury
PubMed: 25287331
DOI: 10.1111/apha.12402 -
Journal of Injury & Violence Research Jul 2015Acute kidney injury (AKI) is a condition that leads to a rapid deterioration of renal function associated with impairment to maintain electrolyte and acid balance, and,... (Review)
Review
BACKGROUND
Acute kidney injury (AKI) is a condition that leads to a rapid deterioration of renal function associated with impairment to maintain electrolyte and acid balance, and, if left untreated, ultimately irreversible kidney damage and renal necrosis. There are a number of causes that can trigger AKI, ranging from underlying conditions as well as trauma and surgery. Specifically, the global rise in surgical procedures led to a substantial increase of AKI incidence rates, which in turn impacts on mortality rates, quality of life and economic costs to the healthcare system. However, no effective therapy for AKI exists. Current approaches, such as pharmacological intervention, help in alleviating symptoms in slowing down the progression, but do not prevent or reverse AKI-induced organ damage.
METHODS
An in-depth understanding of the molecular machinery involved in and modulated by AKI induction and progression is necessary to specifically pharmacologically target key molecules. A major hurdle to devise a successful strategy is the multifactorial and complex nature of the disorder itself, whereby the activation of a number of seemingly independent molecular pathways in the kidney leads to apoptotic and necrotic events.
RESULTS
The renin-angiotensin-aldosterone-system (RAAS) axis appears to be a common element, leading to downstream events such as triggers of immune responses via the NFB pathway. Other pathways intricately linked with AKI-induction and progression are the tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF) signaling cascades, as well as a number of other modulators. Surprisingly, it has been shown that the involvement of the glutamatergic axis, believed to be mainly a component of the neurological system, is also a major contributor.
CONCLUSIONS
Here we address the current understanding of the molecular pathways evoked in AKI, their interplay, and the potential to pharmacologically intervene in the effective prevention and/or progression of AKI.
Topics: Acute Kidney Injury; Apoptosis; Biomarkers; Humans; Metabolic Networks and Pathways; Necrosis; Renin-Angiotensin System; Transforming Growth Factors; Tumor Necrosis Factor-alpha
PubMed: 26104320
DOI: 10.5249/jivr.v7i2.615 -
International Journal of Molecular... Oct 2022The serious clinical course of SARS-CoV-2 infection is usually accompanied by acute kidney injury (AKI), worsening prognosis and increasing mortality. AKI in COVID-19 is... (Review)
Review
The serious clinical course of SARS-CoV-2 infection is usually accompanied by acute kidney injury (AKI), worsening prognosis and increasing mortality. AKI in COVID-19 is above all a consequence of systemic dysregulations leading to inflammation, thrombosis, vascular endothelial damage and necrosis. All these processes rely on the interactions between innate immunity elements, including circulating blood cells, resident renal cells, their cytokine products, complement systems, coagulation cascades and contact systems. Numerous simultaneous pathways of innate immunity should secure an effective host defense. Since they all form a network of cross-linked auto-amplification loops, uncontrolled activation is possible. When the actions of selected pathways amplify, cascade activation evades control and the propagation of inflammation and necrosis worsens, accompanied by complement overactivity and immunothrombosis. The systemic activation of innate immunity reaches the kidney, where the damage affecting single tubular cells spreads through tissue collateral damage and triggers AKI. This review is an attempt to synthetize the connections between innate immunity components engaged in COVID-19-related AKI and to summarize the knowledge on the pathophysiological background of processes responsible for renal damage.
Topics: Humans; COVID-19; SARS-CoV-2; Acute Kidney Injury; Immunity, Innate; Inflammation; Complement System Proteins; Necrosis; Cytokines
PubMed: 36293370
DOI: 10.3390/ijms232012514 -
Critical Care Medicine Apr 2020
Topics: Gangrene; Humans; Ultrasonography
PubMed: 32205631
DOI: 10.1097/CCM.0000000000004240 -
Kidney International Apr 2019Chemotherapy-induced nephrotoxicity limits the success of cancer therapy. Landau et al. now describe a mechanism by which a first dose of cisplatin renders the kidney...
Chemotherapy-induced nephrotoxicity limits the success of cancer therapy. Landau et al. now describe a mechanism by which a first dose of cisplatin renders the kidney sensitive to necroptosis mediated by a second dose. Unresolved injury and sustained necrosis, therefore, may represent a pathophysiological means of transition from acute kidney injury to chronic kidney disease.
Topics: Acute Kidney Injury; Cisplatin; Humans; Kidney; Necrosis; Renal Insufficiency, Chronic
PubMed: 30904060
DOI: 10.1016/j.kint.2018.12.004 -
Nephron 2018Renal tubules represent an intercellular unit and function as a syncytium. When acute tubular necrosis was first visualized to occur through a process of synchronized... (Review)
Review
Renal tubules represent an intercellular unit and function as a syncytium. When acute tubular necrosis was first visualized to occur through a process of synchronized regulated necrosis (SRN) in handpicked primary renal tubules, it became obvious that SRN actually promotes nephron loss. This realization adds to our current understanding of acute kidney injury (AKI)-chronic kidney disease (CKD) transition and argues for the prevention of AKI episodes to prevent CKD progression. Because SRN is triggered by necroptosis and executed by ferroptosis, 2 recently identified signaling pathways of regulated necrosis, a combination therapy employing necrostatins and ferrostatins may be beneficial for protection against nephron loss. Clinical trials in AKI and during the process of kidney transplantation are now required to prevent SRN. Additionally, necrotic cell death drives autoimmunity and necroinflammation and therefore represents a therapeutic target even for the prevention of antibody-mediated rejection of allografts years after the transplantation process.
Topics: Acute Kidney Injury; Apoptosis; Cell Death; Disease Progression; Humans; Kidney; Necrosis; Nephritis
PubMed: 29961062
DOI: 10.1159/000490807 -
BMJ Case Reports Jan 2020Terlipressin is a commonly used drug in hepatology practice for the two most serious complications of cirrhosis, that is, acute oesophageal variceal bleed and...
Terlipressin is a commonly used drug in hepatology practice for the two most serious complications of cirrhosis, that is, acute oesophageal variceal bleed and hepatorenal syndrome. Acute-on-chronic liver failure (ACLF) is a medical emergency and is frequently associated with acute kidney injury (AKI). Two male patients with alcohol-induced ACLF with high MELD (Model for End-Stage Liver Disease) score presented with AKI. Both were treated with terlipressin infusion. There was no response to terlipressin in these sick patients, and further both patients developed ischaemic skin necrosis and succumbed to multiorgan failure. Continuous infusion of terlipressin is superior to bolus dosing, but we noted that continuous infusion might as well be associated with severe adverse effects in patients with a high MELD score. More extensive prospective studies, including patients with high MELD score, are required to ascertain the safety of terlipressin.
Topics: Acute Kidney Injury; Acute-On-Chronic Liver Failure; Diagnosis, Differential; Humans; Ischemia; Male; Middle Aged; Necrosis; Skin Diseases; Terlipressin
PubMed: 31948983
DOI: 10.1136/bcr-2019-233089 -
International Braz J Urol : Official... 2015To investigate the clinical characteristics, prognosis, survival and diagnosis of high-grade primary renal leiomyosarcoma.
OBJECTIVE
To investigate the clinical characteristics, prognosis, survival and diagnosis of high-grade primary renal leiomyosarcoma.
MATERIALS AND METHODS
From January 2003 to April 2013, 10 cases of high-grade primary renal leiomyosarcoma were retrospectively reviewed. We analyzed clinical manifestations, treatment and prognosis of our group and correlated to the literature.
RESULTS
Ten cases (five male and five female patients; age range 43-77 years, mean = 57 ± std d:12.3 ) were enrolled. The mean diameter of the tumor masses was 9.35 ± 4.5 cm (range 3-18 cm). 40% of the patients were asymptomatic while the major symptom of 60% patients was lumbar pain. Nephrectomy was performed in 90% of patients. Partial nephrectomy surgery was preferred for only one patient. Pleomorphism and necrosis with high-grade, pink spindle cell cytoplasm were viewed in all patients. All patients were high-grade, pink spindle cell cytoplasm and pleomorfism and necrosis were observed in all. In an immunohistochemical examination, vimentin was seen in 100%, desmin in 90% and smooth muscle actin in 80% of the patients. CD117 was negative in all patients. All of the cases were followed-up, and the time of survival varied from 6 to 68 months (mean 23.9 ± std d:20.1). No patient received adjuvant CTx and/or RTx.
CONCLUSION
High-grade primary renal leiomyosarcomas (LMSs) are rare and highly malignant and the prognosis is poor. Early diagnosis and radical nephrectomy can prolong the patient's life. Surgery is the main treatment modality for renal (leiomyosarcoma) LMS.
Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Kidney; Kidney Neoplasms; Leiomyosarcoma; Magnetic Resonance Imaging; Male; Middle Aged; Necrosis; Nephrectomy; Prognosis; Retrospective Studies; Tumor Burden
PubMed: 26005972
DOI: 10.1590/S1677-5538.IBJU.2015.02.17 -
The New England Journal of Medicine Nov 2018Among patients with acute myocardial infarction, cardiogenic shock, and multivessel coronary artery disease, the risk of a composite of death from any cause or severe... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Among patients with acute myocardial infarction, cardiogenic shock, and multivessel coronary artery disease, the risk of a composite of death from any cause or severe renal failure leading to renal-replacement therapy at 30 days was found to be lower with percutaneous coronary intervention (PCI) of the culprit lesion only than with immediate multivessel PCI. We evaluated clinical outcomes at 1 year.
METHODS
We randomly assigned 706 patients to either culprit-lesion-only PCI or immediate multivessel PCI. The results for the primary end point of death or renal-replacement therapy at 30 days have been reported previously. Prespecified secondary end points at 1 year included death from any cause, recurrent myocardial infarction, repeat revascularization, rehospitalization for congestive heart failure, the composite of death or recurrent infarction, and the composite of death, recurrent infarction, or rehospitalization for heart failure.
RESULTS
As reported previously, at 30 days, the primary end point had occurred in 45.9% of the patients in the culprit-lesion-only PCI group and in 55.4% in the multivessel PCI group (P=0.01). At 1 year, death had occurred in 172 of 344 patients (50.0%) in the culprit-lesion-only PCI group and in 194 of 341 patients (56.9%) in the multivessel PCI group (relative risk, 0.88; 95% confidence interval [CI], 0.76 to 1.01). The rate of recurrent infarction was 1.7% with culprit-lesion-only PCI and 2.1% with multivessel PCI (relative risk, 0.85; 95% CI, 0.29 to 2.50), and the rate of a composite of death or recurrent infarction was 50.9% and 58.4%, respectively (relative risk, 0.87; 95% CI, 0.76 to 1.00). Repeat revascularization occurred more frequently with culprit-lesion-only PCI than with multivessel PCI (in 32.3% of the patients vs. 9.4%; relative risk, 3.44; 95% CI, 2.39 to 4.95), as did rehospitalization for heart failure (5.2% vs. 1.2%; relative risk, 4.46; 95% CI, 1.53 to 13.04).
CONCLUSIONS
Among patients with acute myocardial infarction and cardiogenic shock, the risk of death or renal-replacement therapy at 30 days was lower with culprit-lesion-only PCI than with immediate multivessel PCI, and mortality did not differ significantly between the two groups at 1 year of follow-up. (Funded by the European Union Seventh Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .).
Topics: Aged; Female; Follow-Up Studies; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Patient Readmission; Percutaneous Coronary Intervention; Recurrence; Renal Insufficiency; Renal Replacement Therapy; Shock, Cardiogenic
PubMed: 30145971
DOI: 10.1056/NEJMoa1808788