scholarly journals Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Benjamin Wilde ◽  
Antonios Katsounas
Keyword(s):  
Liver Cirrhosis ◽  
Systemic Inflammation ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Significant Risk ◽  
Kidney Injury ◽  
Immune Dysfunction ◽  
Developed Countries ◽  
Bacterial Peritonitis ◽  
End Stage

Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world’s most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.

scholarly journals Neutrophils associate with Bowman’s capsule rupture specifically in PR3-ANCA glomerulonephritis

2021 ◽  
Author(s):  
Samy Hakroush ◽  
Björn Tampe
Keyword(s):  
Plasma Cells ◽  
Immune Cell ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Stage Renal Disease ◽  
End Stage ◽  
Bowman's Capsule ◽  
Tubulointerstitial Inflammation ◽  
Capsule Rupture

Abstract Background Renal involvement is a common and severe complication of ANCA (antineutrophil cytoplasmic antibody) associated vasculitis (AAV) potentially resulting in a pauci-immune necrotizing and crescentic antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We recently described that Bowman’s capsule rupture links glomerular damage to tubulointerstitial inflammation in ANCA-associated glomerulonephritis. Herein we provide a comprehensive histological subtyping of immune cell infiltrates in association with Bowman’s capsule rupture in ANCA GN. Methods A total of 44 kidney biopsies with ANCA GN were retrospectively included in a single-center observational study. Within a renal biopsy specimen, each glomerulus was scored separately for the presence of extensive and focal Bowman’s capsule rupture in injured glomeruli. Infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the area of total cortical inflammation. Results Extensive Bowman’s capsule rupture was associated with tubulointerstitial inflammation containing infiltrates of neutrophils, eosinophils and plasma cells. A similar association was observed for the presence of focal Bowman’s capsule rupture, correlating with tubulointerstitial inflammation containing neutrophils, eosinophils and plasma cells. Multiple logistic regression confirmed that extensive Bowman’s capsule rupture correlated with tubulointerstitial inflammation containing neutrophils, and focal Bowman’s capsule rupture correlated with neutrophil and plasma cell infiltration. Furthermore, this association was specifically observed in PR3-ANCA GN. Conclusion To our knowledge, this is the first report linking Bowman’s capsule rupture directly to tubulointerstitial inflammation by immune cell subtypes. This underscores a pathomechanistic link between tubulointerstitial and glomerular lesions in ANCA GN and needs further investigation. Graphical abstract

scholarly journals Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5717 ◽  
Author(s):  
Jung-Yeon Kim ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Therapeutic Option ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Heme Oxygenase 1 ◽  
Anti Inflammatory

Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.

Predictive and Prognostic Value of Ascitic Fluid Mannose‑binding lectin in Patients with Spontaneous Bacterial Peritonitis

2020 ◽  
Vol 19 ◽  
Author(s):  
Amal A. Mohamed ◽  
Mohamed Abdelhamid ◽  
Naglaa El-Toukhy ◽  
Ahmed Sabry ◽  
Rania Abdelmonem Khattab ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Ascitic Fluid ◽  
Spontaneous Bacterial Peritonitis ◽  
Significant Negative Correlation ◽  
Meld Score ◽  
Mannose Binding Lectin ◽  
Bacterial Peritonitis ◽  
Mannose Binding ◽  
End Stage ◽  
Binding Lectin

Background/Aim: Spontaneous bacterial peritonitis is a common bacterial infection of ascitic fluid mainly in ascites due to liver cirrhosis. Mannose-binding lectin (MBL) can activate phagocytosis and the complement system. Spontaneous bacterial peritonitis was detected to be higher in MBL deficiency. This study aimed to assess ascitic fluid MBL in liver cirrhosis and spontaneous bacterial peritonitis. Methods: Ninety patients with cirrhotic ascites were included. Forty five of them had SBP. Child-Pugh score, Model for End Stage Liver Disease (MELD) and its update (uMELD) scores were used to assess severity of liver cirrhosis. Ascitic fluid samples were obtained for differentiation of leucocytic count, estimation of albumin, protein, glucose, and serumascitic albumin gradient. Ascitic fluid levels of MBL were measured for all patients. SBP was documented if polymorphonuclear leucocytic count ≥250/mm in ascitic fluid. Results: Ascitic fluid MBL level was significantly lower in patients with SBP. MBL had a significant negative correlation with ascitic total leukocytic count (TLC), also with serum creatinine, bilirubin, PT, INR and MELD score among SBP patients. However, it had a significant positive correlation with ascitic protein and with platelets. According to multivariate analysis; fever, TLC, platelets, creatinine, MBL, glucose and polymorphs were independent predictors for SBP development. Conclusion: Ascitic fluid MBL could be a good predictive and prognostic marker in patients with cirrhosis and spontaneous bacterial peritonitis.

scholarly journals Predictors of Development of Hepatorenal Syndrome in Hospitalized Cirrhotic Patients with Acute Kidney Injury

2021 ◽  
Vol 10 (23) ◽  
pp. 5621
Author(s):  
Roula Sasso ◽  
Ahmad Abou Yassine ◽  
Liliane Deeb
Keyword(s):  
Acute Kidney Injury ◽  
Spontaneous Bacterial Peritonitis ◽  
Hepatorenal Syndrome ◽  
Kidney Injury ◽  
Alcoholic Cirrhosis ◽  
Clinical Feature ◽  
Decompensated Liver Cirrhosis ◽  
Bacterial Peritonitis ◽  
Cirrhotic Patients ◽  
End Stage

Hepatorenal syndrome (HRS) is a type of acute kidney injury (AKI), occurring in patients with decompensated liver cirrhosis and is associated with high mortality. We aim to describe the predictors associated with the development of HRS in cirrhotic patients with AKI. We retrospectively analyzed 529 cirrhotic patient encounters with AKI across all Northwell Health institutions between 1 January 2015 and 31 December 2018. We performed multivariate analyses to determine independent predictors of development of HRS. Alcoholic cirrhosis was the most common identified etiology of cirrhosis. The mean Model for End-Stage Liver Disease Scorewas18 (±7). Ascites was the most commonly identified clinical feature of portal hypertension. Infection was identified in 38.4% of patients with urinary tract infection/pyelonephritis being the most common. Spontaneous bacterial peritonitis occurred in 5.9% of patients. The most common cause of AKI was pre-renal. Hepatorenal syndrome was identified in 9.8% of patient encounters. Predictors of HRS were history of ascites, serum creatinine >2.5 mg/dL, albumin <3 g/dL, bilirubin >2 mg/dL and spontaneous bacterial peritonitis. We demonstrate strong predictors for the development of HRS which can aid clinicians to attain an early diagnosis of HRS, leading to prompt and targeted management and improving outcomes.

Immune Cells in Ischemic Acute Kidney Injury

2019 ◽  
Vol 20 (8) ◽  
pp. 770-776 ◽  
Author(s):  
Long Zheng ◽  
Wenjun Gao ◽  
Chao Hu ◽  
Cheng Yang ◽  
Ruiming Rong
Keyword(s):  
Acute Kidney Injury ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Systemic Disease ◽  
Kidney Injury ◽  
Repair Process ◽  
Injured Kidney

Acute kidney injury (AKI) is a systemic disease characterized by acute loss of renal function and accumulation of end products of nitrogen metabolism. Ischemic AKI is the most common cause of AKI, and inflammatory responses are inevitablely involved in ischemic AKI. In the process of ischemic AKI, multiple factors are involved in activating and recruitment of immune cell to the injured kidney. These factors include DAMPs and HIFs released from the injured kidney, increased expression of adhesion molecules, the production of chemokines and cytokines, activation of complement system and TLRs as well as the permeability dysfunction of the renal vascular endothelium. Immune cells of both the innate and adaptive immune systems, such as neutrophils, dendritic cells, macrophages and lymphocytes contribute to the pathogenesis of renal injury after ischemia reperfusion injury (IRI), with some of their subpopulations also participating in the repair process. Numerous studies of immune cells involved in the pathogenesis of AKI have enhanced the understanding of their possible mechanisms in AKI which might become the potential targets for the treatment of ischemic AKI. This review describes the function of the immune cells in the pathogenesis and repair of ischemic AKI and emphasizes the treatment of ischemic AKI potentially targeting them.

scholarly journals Rifaximin has the potential to prevent complications of cirrhosis

2018 ◽  
Vol 11 ◽  
pp. 175628481880030 ◽  
Author(s):  
Steven L. Flamm ◽  
Kevin D. Mullen ◽  
Zeev Heimanson ◽  
Arun J. Sanyal
Keyword(s):  
Acute Kidney Injury ◽  
Variceal Bleeding ◽  
Hepatorenal Syndrome ◽  
Kidney Injury ◽  
International Normalized Ratio ◽  
Meld Score ◽  
Bacterial Peritonitis ◽  
Complications Of Cirrhosis ◽  
End Stage ◽  
Post Hoc

Background: Cirrhosis-related complications are associated with poor prognosis. With our analyses, we examined the potential benefit of rifaximin in reducing the risk of developing cirrhosis-related complications. Methods: Adults with cirrhosis and hepatic encephalopathy (HE) in remission were randomly assigned to receive rifaximin 550 mg twice daily or placebo for 6 months with concomitant lactulose permitted. Post hoc analyses examined time to cirrhosis-related complications (HE, spontaneous bacterial peritonitis (SBP), variceal bleeding, acute kidney injury/hepatorenal syndrome). Subgroup analyses evaluated efficacy for select baseline disease characteristics. Results: Of patients receiving rifaximin ( n = 140) and placebo ( n = 159), 53.6% and 49.1%, respectively, had baseline Model for End-Stage Liver Disease (MELD) score ⩾ 12 and international normalized ratio (INR) ⩾ 1.2. Baseline ascites was observed in 36.4% (rifaximin) and 34.6% (placebo) of patients. In patients with MELD score ⩾ 12 and INR ⩾ 1.2, rifaximin reduced the relative risk (RR) of any first complication experienced during trial by 59% [hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.25–0.67; p < 0.001] versus placebo. For patients with baseline ascites, rifaximin reduced the RR of any first complication experienced during trial by 42% versus placebo (HR = 0.58, 95% CI: 0.34–1.0; p = 0.045). For some subgroups, there was a decrease in RR of complications of SBP, variceal bleeding, and acute kidney injury/hepatorenal syndrome with rifaximin versus placebo, although there were few events reported in the study. Conclusion: Rifaximin may reduce the incidence of cirrhosis-related complications and the recurrence of overt HE. [ ClinicalTrials.gov identifier: NCT00298038.]

scholarly journals Impact of dextrose dose on hypoglycemia development following treatment of hyperkalemia

2018 ◽  
Vol 9 (6) ◽  
pp. 323-329 ◽  
Author(s):  
Nicholas Farina ◽  
Christopher Anderson
Keyword(s):  
Blood Glucose ◽  
Insulin Dose ◽  
Significant Risk ◽  
Kidney Injury ◽  
Glucose Levels ◽  
Intravenous Insulin ◽  
Ventricular Dysrhythmias ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Impact

Background: Hyperkalemia is an electrolyte abnormality that may cause ventricular dysrhythmias and cardiac arrest. The presence of hyperkalemia may necessitate prompt treatment via intravenous insulin and dextrose. One notable complication of this therapy is the development of hypoglycemia. Previous trials have examined the impact of altering the insulin dose administered on hypoglycemia development; no trials to date however, have examined the impact of altering the dextrose dose. Methods: This was a multicenter, retrospective, matched cohort study of patients who received intravenous insulin and dextrose for reversal of hyperkalemia. Patients received either 25 g or 50 g of dextrose in addition to 10 units of insulin. Study populations were matched based on preexisting rates of acute kidney injury, end-stage renal disease, and diabetes mellitus. Blood glucose levels were measured at 60 and 240 min following treatment. Results: A total of 240 patients were included in the analysis. At 60 min following treatment, 15.8% of patients who received 25 g of dextrose developed hypoglycemia, as opposed to 8.3% of patients who received 50 g of dextrose ( p = 0.11). Hyperglycemia was more common in patients who received 50 g of dextrose at 60 min posttreatment; however, this difference did not persist at 240 min. Potassium reduction at 60 min did not differ between groups. In patients with a pretreatment blood glucose <110 mg/dl or without diabetes, rates of hypoglycemia were significantly lower when 50 g of dextrose was administered. Conclusion: In the overall patient population, use of 50 g of dextrose instead of 25 g does not reduce hypoglycemia incidence. However, it may be beneficial is select patient populations, such as patients without type 2 diabetes or patients with a baseline blood glucose <110 mg/dl. Administration of 50 g of dextrose did not appear to place patients at significant risk for hyperglycemia however and could be considered during treatment of hyperkalemia.

Immunoglobulin A nephropathy

2018 ◽  
Author(s):  
Kar Neng Lai ◽  
Sydney C. W. Tang
Keyword(s):  
Acute Kidney Injury ◽  
Iga Nephropathy ◽  
Black People ◽  
Immunoglobulin A ◽  
Kidney Injury ◽  
Developed Countries ◽  
Small Vessel Vasculitis ◽  
Older Children ◽  
To Come ◽  
End Stage

Immunoglobulin A (IgA) nephropathy characteristically causes haematuria and may present as a nephritic illness in older children and young adults. However, it may occur at any age and is commonly asymptomatic, associated first with haematuria alone, later progressing in some patients to hypertension, proteinuria, and progressive loss of glomerular filtration. While this evolution is characteristically slow, over decades, in some it is rapid, leading to early end-stage renal failure. It is common for the disease to present late, as advanced renal disease, or malignant hypertension. It may present with acute kidney injury caused by crescentic disease, but acute kidney injury caused by haematuria may be confused clinically with the same. Henoch–Schönlein purpura is a type of small vessel vasculitis that is most commonly seen in children, but which occurs at all ages, that is associated with IgA deposition. In older children and most adults it merges closely into IgA nephropathy after the acute event. Outcomes in adults are less good. IgA nephropathy is the most common type of glomerulonephritis in most developed countries. The disease is more common in men, and appears to be much less common in black people. The detected incidence is strongly influenced by biopsy policies; the lower your threshold to biopsy patients with haematuria, the more of this condition you discover. There are clear genetic tendencies but the strongest risk seems to come from genes in the human leucocyte antigen complex.

scholarly journals Neuroinflammation in cognitive decline post-cardiac surgery (the FOCUS study): an observational study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e044062
Author(s):  
Annemieke M Peters van Ton ◽  
Harmke B. Duindam ◽  
Julia van Tuijl ◽  
Wilson WL Li ◽  
Hendrik-Jan Dieker ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Observational Study ◽  
Systemic Inflammation ◽  
Study Protocol ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Postoperative Cognitive Dysfunction ◽  
Translocator Protein ◽  
Surgical Trauma ◽  
Cerebral Mri

IntroductionPostoperative cognitive dysfunction occurs frequently after coronary artery bypass grafting (CABG). The underlying mechanisms remain poorly understood, but neuroinflammation might play a pivotal role. We hypothesise that systemic inflammation induced by the surgical trauma could activate the innate immune (glial) cells of the brain. This could lead to an exaggerated neuroinflammatory cascade, resulting in neuronal dysfunction and loss of neuronal cells. Therefore, the aims of this study are to assess neuroinflammation in vivo presurgery and postsurgery in patients undergoing major cardiac surgery and investigate whether there is a relationship of neuroinflammation to cognitive outcomes, changes to brain structure and function, and systemic inflammation.Methods and analysisThe FOCUS study is a prospective, single-centre observational study, including 30 patients undergoing elective on-pump CABG. Translocator protein (TSPO) positron emission tomography neuroimaging will be performed preoperatively and postoperatively using the second generation tracer 18F-DPA-714 to assess the neuroinflammatory response. In addition, a comprehensive cerebral MRI will be performed presurgery and postsurgery, in order to discover newly developed brain and vascular wall lesions. Up to 6 months postoperatively, serial extensive neurocognitive assessments will be performed and blood will be obtained to quantify systemic inflammatory responses and peripheral immune cell activation.Ethics and disseminationPatients do not benefit directly from engaging in the study, but imaging neuroinflammation is considered safe and no side effects are expected. The study protocol obtained ethical approval by the Medical Research Ethics Committee region Arnhem-Nijmegen. This work will be published in peer-reviewed international medical journals and presented at medical conferences.Trial registration numberNCT04520802.

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