Elevated plasma thrombomodulin and angiopoietin-2 predict the development of acute kidney injury in patients with acute myocardial infarction

Liu, Kuan-Liang; Lee, Kuang-Tso; Chang, Chih‐Hsiang; Chen, Yung‐Chang; Lin, Shu‐Min; Chu, Pao‐Hsien

doi:10.1186/cc13876

Cited by 43 publications

(42 citation statements)

References 36 publications

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“…Thrombomodulin is shed from activated or damaged endothelial cells, such that circulating sTM likely reflects endothelial dysfunction rather than the anticoagulant activity of membrane‐bound thrombomodulin . Furthermore, our findings are consistent with the limited existing human literature showing the association of sTM, and to a lesser extent protein C, with AKI in critical illness and myocardial infarction populations …”

Section: Discussionsupporting

confidence: 86%

“…In these models increased levels of the antifibrinolytic protein plasminogen activator inhibitior‐1 (PAI‐1) and reduced levels of the endogenous anticoagulant protein C contribute to microvascular thrombin deposition and impaired tissue perfusion . In nontransplant critical illness and myocardial infarction populations, plasma levels of soluble thrombomodulin (sTM) were recently shown to be associated with AKI . sTM is thought to be a marker of endothelial activation—it derives from the release of membrane‐bound thrombomodulin into circulation when endothelial cells are damaged—and one study in sepsis patients showed that sTM was superior to other markers of endothelial injury for predicting AKI .…”

Section: Introductionmentioning

confidence: 99%

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Postreperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation

Forker

Miano

Reilly

et al. 2019

American Journal of Transplantation

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| INTRODUC TI ONPostoperative acute kidney injury (AKI) complicates up to 70% of lung transplants and is associated with increased risk of chronic kidney disease and death for lung transplant recipients. 1 Postlung transplant AKI incidence is 3-to 4-fold higher than after cardiac surgery, despite lower average age and burden of AKI risk factors. 1,2 Nearly half of AKI cases are moderate to severe, with at least a doubling of baseline serum creatinine. 1,3 The mechanisms explaining this high rate and severity of AKI after lung transplantation remain unclear.Molecular markers of posttransplant AKI have not been studied.Animal models of AKI, including ischemia-reperfusion injury, demonstrate that kidney microvascular thrombosis and endothelial activation are critical initial steps leading to interstitial leukocyte infiltration and kidney tubular injury. 4 In these models increased levels of the antifibrinolytic protein plasminogen activator inhibitior-1 (PAI-1) and reduced levels of the endogenous anticoagulant protein Acute kidney injury (AKI) is common after lung transplantation, but molecular markers remain poorly studied. The endothelial activation markers soluble thrombomodulin (sTM), protein C, and plasminogen activator inhibitor-1 (PAI-1) are implicated in kidney microcirculatory injury in animal models of AKI. We tested the association of 6-hour postreperfusion plasma levels of these markers with posttransplant AKI severity in patients enrolled in the Lung Transplant Outcomes Group prospective cohort study at the University of Pennsylvania during two eras: 2004-06 (n = 61) and 2013-15 (n = 67). We defined AKI stage through postoperative day 5 using Kidney Disease Improving Global Outcomes creatinine criteria. We used multivariable ordinal logistic regression to determine the association of each biomarker with AKI, adjusted for primary graft dysfunction and extracorporeal life support. AKI occurred in 57 (45%) patients across both eras: 28 (22%) stage 1, 29 (23%) stage 2-3. Higher sTM and lower protein C plasma levels were associated with AKI stage in each era and remained so in multivariable models utilizing both eras (sTM: OR 1.76 [95% CI 1.19-2.60] per standard deviation, P = .005; protein C: OR 0.54 [1.19-2.60], P = .003). We conclude that 6-hour postreperfusion plasma sTM and protein C levels are associated with early postlung transplant AKI severity. K E Y W O R D S clinical research/practice, epidemiology, kidney failure/injury, lung transplantation/ pulmonology, translational research/science S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Forker CM, Miano TA, Reilly JP, et al. Postreperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation. Am J Transplant.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Postreperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation

Forker

Miano

Reilly

et al. 2019

American Journal of Transplantation

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“…Genetic polymorphisms in the ABO gene have been associated with circulating levels of glycoproteins important in endothelial function and inflammation, including soluble intercellular adhesion molecule-1 (ICAM-1), thrombomodulin, vWF, and the selectins (12,(20)(21)(22)(23). These same proteins have been implicated in the pathogenesis of AKI (24)(25)(26)(27)(28). Although non-O blood types are reported risk factors for MI, VTE, and ARDS, it is unknown if ABO blood type is associated with AKI risk (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

The ABO Histo-Blood Group and AKI in Critically Ill Patients with Trauma or Sepsis

Reilly

Anderson

Mangalmurti

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objective ABO blood types are determined by antigen modifications on glycoproteins and glycolipids and associated with altered plasma levels of inflammatory and endothelial injury markers implicated in AKI pathogenesis. We sought to determine the association of ABO blood types with AKI risk in critically ill patients with trauma or sepsis.Design, setting, participants, & measurements We conducted two prospective cohort studies at an urban, academic, level I trauma center and tertiary referral center; 497 patients with trauma admitted to the surgical intensive care unit between 2005 and 2010 with an injury severity score .15 and 759 patients with severe sepsis admitted to the medical intensive care unit between 2008 and 2013 were followed for 6 days for the development of incident AKI. AKI was defined by Acute Kidney Injury Network creatinine and dialysis criteria.Results Of 497 patients with trauma, 134 developed AKI (27%). In multivariable analysis, blood type A was associated with higher AKI risk relative to type O among patients of European descent (n=229; adjusted risk, 0.28 versus 0.14; risk difference, 0.14; 95% confidence interval, 0.03 to 0.24; P=0.02). Of 759 patients with sepsis, AKI developed in 326 (43%). Blood type A again conferred higher AKI risk relative to type O among patients of European descent (n=437; adjusted risk, 0.53 versus 0.40; risk difference, 0.14; 95% confidence interval, 0.04 to 0.23; P=0.01). Findings were similar when analysis was restricted to those patients who did not develop acute respiratory distress syndrome or were not transfused. We did not detect a significant association between blood type and AKI risk among individuals of African descent in either cohort.Conclusions Blood type A is independently associated with AKI risk in critically ill patients with trauma or severe sepsis of European descent, suggesting a role for ABO glycans in AKI susceptibility.

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“…Patients with multi‐vessel ischemic heart disease have significantly higher level of sTM than those without . Ang‐2 and sTM can serve as independent clinical predictors of the development of AKI in patients with acute myocardial infarction …”

Section: Soluble Thrombomodulinmentioning

confidence: 99%

“…23 Ang-2 and sTM can serve as independent clinical predictors of the development of AKI in patients with acute myocardial infarction. 24…”

Section: Soluble Thrombomodulinmentioning

confidence: 99%

Biomarkers for acute cardiorenal syndrome

2018

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Cardiorenal syndromes are disorders of the heart and kidneys whereby dysfunction in one organ may lead to dysfunction in the other organ. Cardiorenal syndrome type I (CRS I) is defined as acute kidney injury caused by acute cardiac dysfunction such as acute decompensated heart failure and acute coronary syndrome. Traditional markers like serum creatinine may delay the diagnosis of acute kidney injury and provide limited information regarding the underlying pathophysiology in the setting of CRS I. Herein, we briefly review some emerging biomarkers, including brain natriuretic peptide, soluble ST2, angiopoietin, soluble thrombomodulin, neutrophil gelatinase‐associated lipocalin, kidney injury molecule‐1, cystatin C, interleukin‐18 and calprotectin. These biomarkers may help early detecting, differential diagnosis, assessing disease severity and prognosis in patients with CRS I, therefore improve patient management and outcomes.

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Elevated plasma thrombomodulin and angiopoietin-2 predict the development of acute kidney injury in patients with acute myocardial infarction

Cited by 43 publications

References 36 publications

Postreperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation

Postreperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation

The ABO Histo-Blood Group and AKI in Critically Ill Patients with Trauma or Sepsis

Biomarkers for acute cardiorenal syndrome

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