Serum neutrophil gelatinase-associated lipocalin the estimation of hospital prognosis in patients with ST-elevated myocardial infarction.
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ABSTRACT:
SUBMITTER: Karetnikova V
PROVIDER: S-EPMC5524370 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:IntroductionLoss of kidney function is a common feature of COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We tested whether molecular biomarkers of tubular injury measured at hospital admission were associated with acute kidney injury (AKI) in those with COVID-19 infection.MethodsThis is a prospective cohort observational study consisting of 444 consecutive patients with SARS-CoV-2 enrolled in the Columbia University emergency department (ED) at the peak of the pandemic in New York (March 2020-April 2020). Urine and blood were collected simultaneously at hospital admission (median time: day 0, interquartile range: 0-2 days), and urine biomarkers were analyzed by enzyme-linked immunosorbent assay (ELISA) and a novel dipstick. Kidney biopsies were probed for biomarker RNA and for histopathologic acute tubular injury (ATI) scores.ResultsAdmission urinary neutrophil gelatinase-associated lipocalin (uNGAL) level was associated with AKI diagnosis (267 ± 301 vs. 96 ± 139 ng/ml, P < 0.0001) and staging; uNGAL levels >150 ng/ml had 80% specificity and 75% sensitivity to diagnose AKI stages 2 to 3. Admission uNGAL level quantitatively associated with prolonged AKI, dialysis, shock, prolonged hospitalization, and in-hospital death, even when admission SCr level was not elevated. The risk of dialysis increased almost 4-fold per SD of uNGAL independently of baseline SCr, comorbidities, and proteinuria (odds ratio [OR] [95% CI]: 3.59 [1.83-7.45], P < 0.001). In the kidneys of those with COVID-19, NGAL mRNA expression broadened in parallel with severe histopathologic injury (ATI). Conversely, low uNGAL levels at admission ruled out stages 2 to 3 AKI (negative predictive value: 0.95, 95% CI: 0.92-0.97) and the need for dialysis (negative predictive value: 0.98, 95% CI: 0.96-0.99). Although proteinuria and urinary (u)KIM-1 were implicated in tubular injury, neither was diagnostic of AKI stages.ConclusionIn the patients with COVID-19, uNGAL level was quantitatively associated with histopathologic injury (ATI), loss of kidney function (AKI), and severity of patient outcomes.
| S-EPMC8497954 | biostudies-literature
Project description:Neutrophil gelatinase associated lipocalin (NGAL), was originally identified in neutrophil granules as a heterodimer complex with gelatinase B (matrix metalloproteinase 9, MMP9), but more recently has been found to be secreted by damaged epithelial cells. Ngal is a member of the lipocalin family and subsequently named as lipocalin 2 on the basis of structural similarity with other members of the lipocalin family and its potential association with hydrophobic retinol and cholesterol oleate more strongly than their hydrophilic counterparts. In 2002, a landmark paper suggested that Ngal is a bacteriostatic agent which blocks iron acquisition by interacting with a number of bacterial siderophores, especially enterobactin. Since then, more siderophore-carrying functions have been reported than the possibility of hydrophobic ligand transport. In this setting, Ngal was renamed Siderocalin. Functions of siderocalin include not only bacteriostatic activity but potentially as a mediator of cell growth and differentiation; some of these functions appear to be referable to the holo siderocalin:siderophore:iron complex and recent work suggests that metabolic products may act as mammalian siderophores bound by Ngal. While still speculative, it may be that the mammalian siderophores can establish the missing link between Ngal and a number of its functions in vivo. This review provides an overview of the discoveries of the different ligands of Ngal and consequently related functions. Hydrophobic ligands, bacterial siderophores as well as their modified structures (synthetic siderophores), and mammalian siderophores are summarized.
| S-EPMC5014392 | biostudies-literature
Project description:BackgroundPlasma neutrophil gelatinase-associated lipocalin (pNGAL) has been investigated extensively in acute kidney injury. This study investigated its pathophysiological significance and utility as marker for graft failure and mortality in stable kidney transplant recipients (KTR).MethodsBaseline pNGAL was measured in 698 KTR (58% male, age 53 ± 13 years, estimated glomerular filtration rate 52.4 ± 20.4 mL/min/1.73 m2) at median 5.4 (interquartile range 1.8-12.0) years after transplantation, enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study.ResultspNGAL concentrations were higher in males, younger patients, patients with a deceased-donor kidney and higher serum creatinine. Independent of these, pNGAL was positively associated with urinary protein excretion, systemic inflammation parameters and calcineurin inhibitor use. During median follow-up of 5.3 (4.5-6.0) years, death-censored graft failure rates were 3.9%, 7.3% and 25.0% across increasing tertiles of pNGAL (Plog-rank < 0.001). Cox-regression analyses showed no independent associations of pNGAL with mortality, but strong associations with graft failure (hazard ratio, per doubling 4.16; 95% confidence interval 3.03-5.71; P < 0.001), which remained independent of adjustment for confounders. These associations were present only in patients with pre-existent proteinuria and poor kidney function.ConclusionspNGAL is associated with parameters of kidney graft damage and with graft failure. The latter association is particularly present in KTR with pre-existent poor kidney function and proteinuria. Trial Registration: ClinicalTrials.gov NCT02811835.
| S-EPMC8824800 | biostudies-literature
Project description:Leukocyte-mediated inflammation is central in atherothrombosis and ST-segment elevation myocardial infarction (STEMI). Neutrophil extracellular traps (NETs) have been shown to enhance atherothrombosis and stimulate fibroblast function. We analyzed the effects of NETs on cardiac remodeling after STEMI. We measured double-stranded (ds)DNA and citrullinated histone H3 (citH3) as NET surrogate markers in human culprit site and femoral blood collected during primary percutaneous coronary intervention (n = 50). Fibrocytes were characterized in whole blood by flow cytometry, and in culprit site thrombi and myocardium by immunofluorescence. To investigate mechanisms of fibrocyte activation, isolated NETs were used to induce fibrocyte responses in vitro. Enzymatic infarct size was assessed using creatine-phosphokinase isoform MB area under the curve. Left ventricular function was measured by transthoracic echocardiography. NET surrogate markers were increased at the culprit site compared to the femoral site and were positively correlated with infarct size and left ventricular dysfunction at follow-up. In vitro, NETs promoted fibrocyte differentiation from monocytes and induced fibrocyte activation. Highly activated fibrocytes accumulated at the culprit site and in the infarct transition zone. Our data suggest that NETs might be important mediators of fibrotic remodeling after STEMI, possibly by stimulating fibrocytes.
| S-EPMC6647191 | biostudies-literature
Project description:Human neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein present in a wide variety of tissues and cell types. It exists as a monomer of 25 kDa, a homodimer of 45 kDa or a heterodimer of 135 kDa (disulfide bound to latent matrix metalloproteinase-9). NGAL is considered the biochemical gold standard for the early diagnosis of acute kidney injury and has attracted much attention as a diagnostic biomarker. NGAL has controversial (i.e. both beneficial and detrimental) effects on cellular processes associated with tumor development, such as cell proliferation, survival, migration, invasion and drug resistance. Therefore, the present review aimed at clarifying the role of NGAL in renal cell carcinoma (RCC). Relevant studies of NGAL and RCC were searched in PubMed and relevant information about the structure, expression, function and mechanism of NGAL in RCC were summarized. Finally, the following conclusions could be drawn from the literature: i) NGAL can be detected in cancer tissues, serum and urine of patients with RCC; ii) NGAL is not a suitable diagnostic marker for early screening of RCC; iii) NGAL expression may be used to predict the prognosis of patients with RCC; and iv) Further research on NGAL may be helpful to decrease sunitinib resistance and find new treatment strategies for RCC.
| S-EPMC7798090 | biostudies-literature
Project description:Cancer remains one of the major cause of death in the Western world. Although, it has been demonstrated that new therapies can improve the outcome of cancer patients, still many patients relapse after treatment. Therefore, there is a need to identify novel factors involved in cancer development and/or progression. Recently, neutrophil gelatinase-associated lipocalin (NGAL) has been suggested as a key player in different cancer types. Its oncogenic effect may be related to the complex NGAL/MMP-9. In the present study, NGAL was analyzed at both transcript and protein levels in different cancer types by analysing 38 public available microarray datasets and the Human Protein Atlas tool. NGAL transcripts were significantly higher in the majority of solid tumors compared to the relative normal tissues for every dataset analyzed. Furthermore, concordance of NGAL at both mRNA and protein levels was observed for 6 cancer types including bladder, colorectal, liver, lung, ovarian, and pancreatic. All metastatic tumors showed a decrease of NGAL expression when compared to matched primary lesions. According to these results, NGAL is a candidate marker for tumor growth in a fraction of solid tumors. Further investigations are required to elucidate the function of NGAL in tumor development and metastatic processes.
| S-EPMC4039233 | biostudies-literature
Project description:BackgroundIn-hospital left ventricular (LV) thrombus following acute ST-elevation myocardial infarction (STEMI) has not been evaluated on a national scale and was the focus of this investigation.MethodsWe used the 2003 to 2013 Nationwide Inpatient Sample database to identify adults ?18?years old with a principal diagnosis code of ST-elevation myocardial infarction. Patients were divided into two groups defined by the presence or absence of LV thrombus. Clinical characteristics and in-hospital outcomes were studied using relevant statistics. Multiple linear and logistic regression models were conducted to identify factors associated with LV thrombus.ResultsOf 1,035,888 STEMI patients hospitalized in the U. S from 2003 to 2013, 1982 (0.2%) developed acute in-hospital LV thrombus. Compared to no LV thrombus, patients with LV thrombus were more likely to have in-hospital complications; acute ischemic and hemorrhagic stroke, acute renal failure, gastrointestinal bleed, cardiogenic shock, in-hospital cardiac arrest and mortality. They also had longer mean length of stay and higher hospital charges. Factors associated with LV thrombus included: anterior/anterolateral STEMI, acute or chronic heart failure with reduced ejection fraction, atrial fibrillation, LV aneurysm, Left heart valvular disease, acute or chronic deep venous thrombosis/pulmonary embolism and alcohol abuse. Patients with LV thrombus were less likely to be female [AOR 0.66, 95% CI (0.51-0.84)].ConclusionThe identification of factors associated with early development of LV thrombus following STEMI, will help direct resources for specific high-risk group and prompt cost-effective therapies. Gender variability in LV thrombus development warrants further investigations.
| S-EPMC6891157 | biostudies-literature
Project description:BackgroundIn-hospital ischemic stroke following acute ST-elevation myocardial infarction (STEMI) has not been evaluated on a national scale in the United States.MethodsWe used 2003 to 2014 Nationwide Inpatient Sample data to identify adults with a principal diagnosis of STEMI. Patients were divided into two groups defined by presence or absence of ischemic stroke. Clinical characteristics and in-hospital outcomes were studied using relevant statistics. Multiple linear and logistic regression models identified factors associated with ischemic stroke, national trend of in-hospital stroke incidence and in-hospital mortality.ResultsOf 1,842,529 STEMI patients hospitalized from 2003 to 2014, 22,268 (1.2%) developed acute in-hospital ischemic stroke. Those with acute strokes were older (age ≥ 65 years: 70% vs 46%), more likely female (51% vs 33%), and had higher rates of atrial fibrillation (28.9% vs 12.2%) and heart failure (40.5% vs 21.1%). Age and gender adjusted incidence of in-hospital ischemic stroke following STEMI remained stable; 1.4% in 2003 and 1.5% in 2014 (P trend = 0.50). However, age and gender adjusted in-hospital mortality declined in STEMI patients with and without in-hospital ischemic stroke [AOR 0.97 (0.95-0.99) P trend = 0.03, and AOR 0.98 (0.98-0.99) P trend < 0.001, respectively]. Patients with ischemic strokes had higher in-hospital mortality (25.7% Vs 7.2%, p < 0.001), [AOR 2.11, 95% CI (1.92-2.32)].ConclusionIn the United States, the incidence of acute in-hospital stroke remained stable from 2003 to 2014 following STEMI with significant decrease of in-hospital mortality trends. Despite slight improvement in mortality trends, in-hospital mortality rates remained elevated calling for interventions to optimize health care delivery.
| S-EPMC7736913 | biostudies-literature
Project description:ST segment elevation myocardial infarction remains a significant contributor to morbidity and mortality worldwide, despite a declining incidence and better survival rates. It usually results from thrombotic occlusion of a coronary artery at the site of a ruptured or eroded plaque. Diagnosis is based on characteristic symptoms and electrocardiogram changes, and confirmed subsequently by raised cardiac enzymes. Prognosis is dependent on the size of the infarct, presence of collaterals and speed with which the occluded artery is reopened. Mechanical reperfusion by primary percutaneous coronary intervention is superior to fibrinolytic therapy if delivered by an experienced team in a timely fashion. Post-reperfusion care includes monitoring for complications, evaluation of left ventricular function, secondary preventive therapy and cardiac rehabilitation.
| S-EPMC5922709 | biostudies-other
Project description:NGAL (human neutrophil gelatinase-associated lipocalin) and its mouse analogue 24p3 are members of the lipocalin family of small secreted proteins. These proteins are up-regulated in a number of pathological conditions, including cancers, and may function as transporters of essential factors. Although previous publications have suggested that 24p3 has pro-apoptotic functions, other data are more suggestive of a survival function. The current study was designed to determine whether NGAL is pro- or anti-apoptotic. Apoptosis induced in human adenocarcinoma A549 cells by the 5-lipoxygenase-activating-protein inhibitor MK886, or several celecoxib-derived PDK1 (phosphoinositide-dependent kinase 1) inhibitors that are devoid of cyclo-oxygenase-2 inhibitory activity, was accompanied by a dose- and time-dependent increase of NGAL mRNA levels, as was reported previously with 24p3. A similar induction of NGAL mRNA was observed in human breast cancer MCF7 cells treated with MK886, indicating this was not a cell-specific effect. Treatment of A549 cells with up to 150 mug/10(6) cells of purified recombinant NGAL protein had no effect on viability, whereas antisera against the full-length NGAL protein induced apoptosis in these cells. The stable overexpression of NGAL in A549 cells had no effect on proliferation or viability. However, the cell death induced by a PDK1 inhibitor was reduced by 50% in NGAL-overexpressing cells. Decreasing NGAL mRNA and protein expression with siRNA (small interfering RNA) in A549 cells increased the toxicity of a PDK1 inhibitor by approx. 45%. These data indicate that, although the induction of NGAL correlates with apoptosis, this induction represents a survival response. Because NGAL is a secreted protein, it may play an extracellular role in cell defence against toxicants and/or facilitate the survival of the remaining cells.
| S-EPMC1276944 | biostudies-other