Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin

Abstract Background Endothelial activation and damage occur early during sepsis, with activated coagulopathy and playing a major role in the pathophysiology of sepsis-induced acute kidney injury (AKI). The aim of this study was to compare the various biomarkers of endothelial injury with the biomark...

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Main Authors: Shinshu Katayama, Shin Nunomiya, Kansuke Koyama, Masahiko Wada, Toshitaka Koinuma, Yuya Goto, Ken Tonai, Jun Shima
Format: Article
Language:English
Published: BMC 2017-08-01
Series:Critical Care
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13054-017-1815-x
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author Shinshu Katayama
Shin Nunomiya
Kansuke Koyama
Masahiko Wada
Toshitaka Koinuma
Yuya Goto
Ken Tonai
Jun Shima
author_facet Shinshu Katayama
Shin Nunomiya
Kansuke Koyama
Masahiko Wada
Toshitaka Koinuma
Yuya Goto
Ken Tonai
Jun Shima
author_sort Shinshu Katayama
collection DOAJ
description Abstract Background Endothelial activation and damage occur early during sepsis, with activated coagulopathy and playing a major role in the pathophysiology of sepsis-induced acute kidney injury (AKI). The aim of this study was to compare the various biomarkers of endothelial injury with the biomarkers of coagulation and inflammation and to determine a significant predictor of AKI in patients with sepsis. Methods We conducted a single-center, retrospective, observational study on patients with sepsis fulfilling the Third International Consensus Definitions for Sepsis and Septic Shock criteria admitted to an adult intensive care unit (ICU) at a university hospital from June 2011 to December 2016. Levels of 13 biomarkers were measured on ICU admission, including markers of endothelial injury (soluble thrombomodulin [sTM], E-selectin, protein C, and plasminogen activator inhibitor-1 [PAI-1]) and markers of coagulation derangement (platelet count, fibrin degradation product [FDP], prothrombin time [PT], fibrinogen, α2-plasminogen inhibitor [α2-PI], antithrombin III [AT III], plasminogen, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex). All patients with sepsis were reviewed, and the development of AKI was evaluated. Multivariate logistic regression analysis was performed to identify significant independent predictive factors for AKI. Results Of the 514 patients admitted with sepsis, 351 (68.3%) developed AKI. Compared with the non-AKI group, all the endothelial biomarkers were significantly different in the AKI group (sTM [23.6 vs. 15.6 U/ml, P < 0.0001], E-selectin [65.5 vs. 46.2 ng/ml, P = 0.0497], PAI-1 [180.4 vs. 75.3 ng/ml, P = 0.018], and protein C [45.9 vs. 58.7 ng/ml, P < 0.0001]). Biomarkers of coagulopathy and inflammation, platelet counts, FDP, PT, α2-PI, AT III, plasminogen, and C-reactive protein were significantly different between the two groups. Multivariable logistic regression analysis showed that sTM was an independent predictive factor of AKI, with an AUROC of 0.758 (P < 0.0001). Conclusions Endothelial biomarkers were significantly changed in the sepsis patients with AKI. Particularly, sTM was an independent predictive biomarker for the development of AKI that outperformed other coagulation and inflammation biomarkers as well as organ function in patients with sepsis.
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spelling doaj.art-757098dc48844269852a744aa832b6e42022-12-22T03:16:02ZengBMCCritical Care1364-85352017-08-012111910.1186/s13054-017-1815-xMarkers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulinShinshu Katayama0Shin Nunomiya1Kansuke Koyama2Masahiko Wada3Toshitaka Koinuma4Yuya Goto5Ken Tonai6Jun Shima7Division of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of MedicineDivision of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of MedicineDivision of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of MedicineDivision of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of MedicineDivision of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of MedicineDivision of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of MedicineDivision of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of MedicineDivision of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of MedicineAbstract Background Endothelial activation and damage occur early during sepsis, with activated coagulopathy and playing a major role in the pathophysiology of sepsis-induced acute kidney injury (AKI). The aim of this study was to compare the various biomarkers of endothelial injury with the biomarkers of coagulation and inflammation and to determine a significant predictor of AKI in patients with sepsis. Methods We conducted a single-center, retrospective, observational study on patients with sepsis fulfilling the Third International Consensus Definitions for Sepsis and Septic Shock criteria admitted to an adult intensive care unit (ICU) at a university hospital from June 2011 to December 2016. Levels of 13 biomarkers were measured on ICU admission, including markers of endothelial injury (soluble thrombomodulin [sTM], E-selectin, protein C, and plasminogen activator inhibitor-1 [PAI-1]) and markers of coagulation derangement (platelet count, fibrin degradation product [FDP], prothrombin time [PT], fibrinogen, α2-plasminogen inhibitor [α2-PI], antithrombin III [AT III], plasminogen, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex). All patients with sepsis were reviewed, and the development of AKI was evaluated. Multivariate logistic regression analysis was performed to identify significant independent predictive factors for AKI. Results Of the 514 patients admitted with sepsis, 351 (68.3%) developed AKI. Compared with the non-AKI group, all the endothelial biomarkers were significantly different in the AKI group (sTM [23.6 vs. 15.6 U/ml, P < 0.0001], E-selectin [65.5 vs. 46.2 ng/ml, P = 0.0497], PAI-1 [180.4 vs. 75.3 ng/ml, P = 0.018], and protein C [45.9 vs. 58.7 ng/ml, P < 0.0001]). Biomarkers of coagulopathy and inflammation, platelet counts, FDP, PT, α2-PI, AT III, plasminogen, and C-reactive protein were significantly different between the two groups. Multivariable logistic regression analysis showed that sTM was an independent predictive factor of AKI, with an AUROC of 0.758 (P < 0.0001). Conclusions Endothelial biomarkers were significantly changed in the sepsis patients with AKI. Particularly, sTM was an independent predictive biomarker for the development of AKI that outperformed other coagulation and inflammation biomarkers as well as organ function in patients with sepsis.http://link.springer.com/article/10.1186/s13054-017-1815-xAcute kidney injuryEndothelial injuryE-selectinSepsisSoluble thrombomodulinPlasminogen activator inhibitor-1
spellingShingle Shinshu Katayama
Shin Nunomiya
Kansuke Koyama
Masahiko Wada
Toshitaka Koinuma
Yuya Goto
Ken Tonai
Jun Shima
Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin
Critical Care
Acute kidney injury
Endothelial injury
E-selectin
Sepsis
Soluble thrombomodulin
Plasminogen activator inhibitor-1
title Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin
title_full Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin
title_fullStr Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin
title_full_unstemmed Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin
title_short Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin
title_sort markers of acute kidney injury in patients with sepsis the role of soluble thrombomodulin
topic Acute kidney injury
Endothelial injury
E-selectin
Sepsis
Soluble thrombomodulin
Plasminogen activator inhibitor-1
url http://link.springer.com/article/10.1186/s13054-017-1815-x
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