Angiopoietin/Tie2 Dysbalance Is Associated with Acute Kidney Injury after Cardiac Surgery Assisted by Cardiopulmonary Bypass

Introduction The pathophysiology of acute kidney injury (AKI) after cardiac surgery is not completely understood. Recent evidence suggests a pivotal role for the endothelium in AKI. In experimental models of AKI, the endothelial specific receptor Tie2 with its ligands Angiopoietin (Ang) 1 and Ang2 are deranged. This study investigates their status after cardiac surgery, and a possible relation between angiopoietins and AKI. Methods From a cohort of 541 patients that underwent cardiac surgery, blood and urine was collected at 5 predefined time points. From this cohort we identified 21 patients who had at least 50% post-operative serum creatinine increase (AKI). We constructed a control group (n = 21) using propensity matching. Systemic levels of Ang1, Ang2, and sTie2 were measured in plasma and the AKI markers albumin, kidney injury molecule-1 (KIM-1) and N-acetyl-beta-D-glucosaminidase (NAG) were measured in the urine. Results Ang2 plasma levels increased over time in AKI (from 4.2 to 11.6 ng/ml) and control patients (from 3.0 to 6.7 ng/ml). Ang2 levels increased 1.7-fold more in patients who developed AKI after cardiac surgery compared to matched control patients. Plasma levels of sTie2 decreased 1.6-fold and Ang1 decreased 3-fold over time in both groups, but were not different between AKI and controls (Ang1 P = 0.583 and sTie2 P = 0.679). Moreover, we found a positive correlation between plasma levels of Ang2 and urinary levels of NAG. Conclusions The endothelial Ang/Tie2 system is in dysbalance in patients that develop AKI after cardiac surgery compared to matched control patients.

• Publication year

  2015

• Venue

  PLoS ONE

• Publication date

  2015-08-26

• Fields of study

  Medicine

• Identifiers
  DOI 10.1371/journal.pone.0136205PMID 26309217PMCID 4550386
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Effects of cell-saving devices and filters on transfusion in cardiac surgery: a multicenter randomized study.

  2015cited by this paper
• Abrupt Reflow Enhances Cytokine-Induced Proinflammatory Activation of Endothelial Cells During Simulated Shock and Resuscitation

  2014cited by this paper
• The renal angiopoietin/Tie2 system in lethal human sepsis

  2014cited by this paper
• Acute kidney injury after on-pump or off-pump coronary artery bypass grafting in elderly patients.

  2014cited by this paper
• Small acute increases in serum creatinine are associated with decreased long-term survival in the critically ill.

  2014cited by this paper
• Lung-Targeted RNA Interference Against Angiopoietin-2 Ameliorates Multiple Organ Dysfunction and Death in Sepsis

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• Dysregulation of the angiopoietin–Tie-2 axis in sepsis and ARDS

  2013cited by this paper
• Pleiotropic effects of angiopoietin-2 deficiency do not protect mice against endotoxin-induced acute kidney injury.

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  2013cited by this paper
• A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ill patients

  2012cited by this paper
• Effect of frozen storage on urinary concentration of kidney damage markers.

  2012cited by this paper
• Angiopoietin-2 levels predict mortality in CKD patients.

  2012cited by this paper
• Angiopoietin-2 is a potential mediator of endothelial barrier dysfunction following cardiopulmonary bypass.

  2012influential reference
• Acute administration of recombinant Angiopoietin-1 ameliorates multiple-organ dysfunction syndrome and improves survival in murine sepsis.

  2011cited by this paper
• The microvascular endothelial cell in shock

  2011cited by this paper
• Albuminuria, proteinuria, and novel urine biomarkers as predictors of long-term allograft outcomes in kidney transplant recipients.

  2011cited by this paper
• Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome

  2010cited by this paper
• Circulating angiopoietin-2 levels increase with progress of chronic kidney disease.

  2010cited by this paper
• Postoperative renal dysfunction and preoperative left ventricular dysfunction predispose patients to increased long-term mortality after coronary artery bypass graft surgery.

  2009cited by this paper
• Time course of angiopoietin-2 release during experimental human endotoxemia and sepsis

  2009cited by this paper
• Alteration of microvascular permeability in acute kidney injury.

  2009cited by this paper
• COMP-angiopoietin-1 decreases lipopolysaccharide-induced acute kidney injury.

  2009cited by this paper
• Shock-induced stress induces loss of microvascular endothelial Tie2 in the kidney which is not associated with reduced glomerular barrier function.

  2009cited by this paper
• Plasma angiopoietin-2 levels increase in children following cardiopulmonary bypass

  2008cited by this paper
• The RIFLE criteria and mortality in acute kidney injury: A systematic review.

  2008cited by this paper
• EARLY ORGAN-SPECIFIC ENDOTHELIAL ACTIVATION DURING HEMORRHAGIC SHOCK AND RESUSCITATION

  2007cited by this paper
• Angiopoietin-2 sensitizes endothelial cells to TNF-α and has a crucial role in the induction of inflammation

  2006cited by this paper
• Angiopoietins: a link between angiogenesis and inflammation.

  2006cited by this paper
• The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies.

  2004cited by this paper
• Tumor Necrosis Factor-α Upregulates Angiopoietin-2 in Human Umbilical Vein Endothelial Cells

  2000cited by this paper
• Tumor necrosis factor-alpha upregulates angiopoietin-2 in human umbilical vein endothelial cells.

  2000cited by this paper
• The role of nitric oxide in cardiac surgery

  1997cited by this paper
• Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues.

  1997cited by this paper
• Effects of tumour necrosis factor and related cytokines on vascular endothelial cells.

  1987cited by this paper
• Urinary albumin determination by the immediate bromcresol green method.

  1978cited by this paper

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  2024cites this paper
• The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI): a meta-analysis

  2024cites this paper
• Modulation of angiopoietin-2 and Tie2: Organ specific effects of microvascular leakage and edema in mice.

  2024cites this paper
• Role of Angiopoietin/Tie2 System in Sepsis: A Potential Therapeutic Target

  2024cites this paper
• Angiopoietin as a Novel Prognostic Marker in Kidney Disease

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• Impact of Angiopoietin-2 on Kidney Diseases

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  2023cites this paper
• Endothelial Permeability and the Angiopoietin/Tie2 System Following Mild and Severe COVID-19

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• Fluid Overload Precedes and Masks Cryptic Kidney Injury in Pediatric Acute Respiratory Distress Syndrome

  2023cites this paper
• Neurodevelopmental Outcomes in Infants with Cardiac Surgery Associated Acute Kidney Injury.

  2022cites this paper
• Histone Deacetylase-6 Modulates the Effects of 4oC Platelets on Vascular Endothelial Permeability.

  2022cites this paper
• Organ Crosstalk in Acute Kidney Injury: Evidence and Mechanisms

  2022cites this paper
• The Neglected Price of Pediatric Acute Kidney Injury: Non-renal Implications

  2022cites this paper
• Changes in Plasma Angiopoietin Levels After Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement: A Prospective Cohort Study.

  2021cites this paper
• The effect of targeting Tie2 on hemorrhagic shock-induced renal perfusion disturbances in rats

  2021cites this paper
• Therapeutic interventions to restore microcirculatory perfusion following experimental hemorrhagic shock and fluid resuscitation: A systematic review

  2020cites this paper
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  2020cites this paper
• The Angiopoietin-Tie2 Pathway in Critical Illness.

  2020cites this paper
• Altered kinetics of circulating progenitor cells in cardiopulmonary bypass (CPB) associated vasoplegic patients: A pilot study

  2020cites this paper
• Genetic variation implicates plasma angiopoietin-2 in the development of acute kidney injury sub-phenotypes

  2020cites this paper
• Biomarkers of Acute Kidney Injury after Cardiac Surgery : A Narrative

  2019cites this paper
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  2019cites this paper
• Fibroblast growth factor 23, endothelium biomarkers and acute kidney injury in critically-ill patients

  2019cites this paper
• Angiopoietin‐2 as a predictor of acute kidney injury in critically ill patients and association with ARDS

  2019cites this paper
• Identification of Acute Kidney Injury Subphenotypes with Differing Molecular Signatures and Responses to Vasopressin Therapy

  2019cites this paper
• Biomarkers of Acute Kidney Injury after Cardiac Surgery: A Narrative Review

  2019cites this paper
• Evaluation of Endothelial Biomarkers on the Prognosis of Patients on Extracorporeal Membrane Oxygenation

  2018cites this paper
• Endothelial dysfunction following coronary artery bypass grafting

  2018cites this paper
• Vasculotide, an angiopoietin‐1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats

  2018cites this paper
• Toxicity study of oxalicumone A, derived from a marine-derived fungus Penicillium oxalicum, in cultured renal epithelial cells

  2017cites this paper
• External validation of predictive models for acute kidney injury following cardiac surgery: A prospective multicentre cohort study

  2017cites this paper
• Systemic angiopoietin-1/2 dysregulation following cardiopulmonary bypass in adults

  2017cites this paper
• Circulating levels of soluble Fas (sCD95) are associated with risk for development of a nonresolving acute kidney injury subphenotype

  2017cites this paper
• Association of markers of endothelial dysregulation Ang1 and Ang2 with acute kidney injury in critically ill patients

  2016cites this paper
• Angiopoietin Balance in Septic Shock Patients With Acute Kidney Injury: Effects of Direct Hemoperfusion With Polymyxin B‐Immobilized Fiber

  2016cites this paper
• Update on perioperative acute kidney injury

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  2016cites this paper