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      Post-reperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation

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          Abstract

          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 post-reperfusion plasma levels of these markers with post-transplant 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 post-operative 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=0.005; protein C: OR 0.54 (1.19–2.60), p=0.003). We conclude that 6-hour post-reperfusion plasma sTM and protein C levels are associated with early post-lung transplant AKI severity.

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          Author and article information

          Journal
          100968638
          29770
          Am J Transplant
          Am. J. Transplant.
          American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
          1600-6135
          1600-6143
          6 June 2019
          23 May 2019
          August 2019
          01 August 2020
          : 19
          : 8
          : 2366-2373
          Affiliations
          [1 ]Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
          [2 ]Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
          [3 ]Division of Cardiovascular Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
          [4 ]Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
          Author notes

          Author contributions

          Study design—CMF, JPR, JMD, JDC, MGSS; study conduct—CMF, TAM, MO, MKP, EEC, LBW, JMD, JDC, MGSS; analysis—CMF, TAM, JPR, LBW, JMD, JDC, MGSS; drafting of manuscript—CMF, MGSS; critical review of manuscript—all authors.

          Correspondence: Michael G. S. Shashaty, shashatm@ 123456pennmedicine.upenn.edu
          Article
          PMC6658345 PMC6658345 6658345 nihpa1034417
          10.1111/ajt.15402
          6658345
          31017370
          6a25db28-a64b-44f1-b37b-8f4ec48a66aa
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