University of Oulu

Inkinen, N., Pettilä, V., Lakkisto, P. et al. Association of endothelial and glycocalyx injury biomarkers with fluid administration, development of acute kidney injury, and 90-day mortality: data from the FINNAKI observational study. Ann. Intensive Care 9, 103 (2019).

Association of endothelial and glycocalyx injury biomarkers with fluid administration, development of acute kidney injury, and 90-day mortality : data from the FINNAKI observational study

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Author: Inkinen, Nina1,2; Pettilä, Ville2; Lakkisto, Päivi3,4;
Organizations: 1Department of Anesthesia and Intensive Care, Central Finland Central Hospital, Central Finland Health Care District, Keskussairaalantie 19 M rak 2krs, 40620, Jyväskylä, Finland
2Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
3Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
4Minerva Foundation Institute for Medical Research, Helsinki, Finland
5Department of Intensive Care, University of Tampere and Tampere University Hospital, Tampere, Finland
6Department on Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland
7Department of Anaesthesia and Intensive Care Medicine, Turku University Hospital, Turku, Finland
8Research Group of Surgery, Anesthesiology and Intensive Care Medicine and Medical Research Center, Oulu University Hospital, Oulu University, Oulu, Finland
9Department of Intensive Care, Austin Hospital, Melbourne, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Springer Nature, 2019
Publish Date: 2020-04-24


Background: Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality.

Results: SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p < 0.001) and IL-6 increased (p < 0.001) with increasing amounts of administered fluid, but other biomarkers did not show differences according to fluid administration. In linear regression models adjusted for IL-6, only VAP-1 was significantly associated with fluid administration on day 1 (p < 0.001) and the cumulative fluid balance on day 5/ICU discharge (p = 0.001). Of 415 patients admitted without AKI, altogether 112 patients (27.0%) developed AKI > 12 h from ICU admission (AKI>12 h). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI>12 h with OR (95% CI) of 12.71 (2.96–54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31–3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29–23.57], p < 0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44–4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67–11.79; p < 0.001) for 90-day mortality.

Conclusions: VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality.

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Series: Annals of intensive care
ISSN: 2110-5820
ISSN-E: 2110-5820
ISSN-L: 2110-5820
Volume: 9
Issue: 1
Article number: 103
DOI: 10.1186/s13613-019-0575-y
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
Funding: The study has been supported by the Academy of Finland, the Sigrid Juselius Foundation, Päivikki and Sakari Sohlberg Foundation, and Institutional Grants from the Helsinki University Hospital (TYH2013343, TYH2016243, TYH 2017241). STV has received a Fellowship Grant from the Sigrid Juselius Foundation and funding for Clinical Researchers (317061) from the Academy of Finland.
Copyright information: © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.