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Endothelial Glycocalyx Shedding Predicts Donor Organ Acceptability and Is Associated With Primary Graft Dysfunction in Lung Transplant Recipients

Sladden, Timothy M., MBBS, BVSc1,2; Yerkovich, Stephanie, PhD1,2; Grant, Michelle, RN1; Zhang, Fuming, PhD3,4; Liu, Xinyue, PhD3,4; Trotter, Michael, MBBS1,2; Hopkins, Peter, MBBS1,2; Linhardt, Robert J., PhD3,4; Chambers, Daniel C., MD1,2

doi: 10.1097/TP.0000000000002539
Original Clinical Science—General
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Background. The endothelial glycocalyx, a sieve-like structure located on the luminal surface of all blood vessels, has been found to be integral to regulation of capillary permeability and mechanotransduction. Given this, we investigated the role of endothelial glycocalyx breakdown products in organ donors and recipients in terms of acceptability for transplant and risk of primary graft dysfunction (PGD).

Methods. Endothelial glycocalyx breakdown products were measured in the peripheral blood of 135 intended and actual organ donors. Breakdown product levels were tested for association with donor demographic and clinical data, organ acceptability for transplant along with lung recipient outcomes (n = 35). Liquid chromatography mass spectrometry analysis was performed to confirm glycosaminoglycan levels and sulfation patterns on donor samples (n = 15). In transplant recipients (n = 50), levels were measured pretransplant and daily for 4 days posttransplant. Levels were correlated with PGD severity and intubation time.

Results. Decreased hyaluronan levels in peripheral blood independently predicted organ acceptability in intended and actual donors (odds ratio, 0.96; [95% confidence interval, 0.93–0.99] P = 0.026). Furthermore, high donor syndecan-1 levels were associated with PGD in recipients (3142 [1575–4829] versus 6229 [4009–8093] pg/mL; P = 0.045). In recipient blood, levels of syndecan-1 were correlated with severe (grades 2–3) PGD at 72 hours posttransplant (5982 [3016–17191] versus 3060 [2005–4824] pg/mL; P = 0.01).

Conclusions. Endothelial glycocalyx breakdown occurs in lung transplant donors and recipients and predicts organ acceptability and development of PGD. Glycocalyx breakdown products may be useful biomarkers in transplantation, and interventions to protect the glycocalyx could improve transplant outcomes.

1 Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia.

2 Faculty of Medicine, The University of Queensland, Brisbane, Australia.

3 Departments of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, NY.

4 Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, NY.

Received 8 July 2018. Revision received 6 November 2018.

Accepted 6 November 2018.

T.M.S. contributed to research design, performance of the research, data analysis, and writing of the paper. S.Y. and D.C.C. contributed equally to research design, data analysis, and writing of the paper. M.G., M.T., and P.H. contributed to data collection and/or analysis and critical revision of the manuscript. X.L. and F.Z. contributed to performance of research, data analysis, and writing of the article. R.J.L. contributed to analytic tools, data analysis, and writing of the article.

The authors declare no conflicts of interest.

This work was supported by a Program Grant from the Prince Charles Hospital Foundation and National Health and Medical Research Council Project Grant (1103862). Neither funding source was involved in the research or manuscript preparation.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Daniel Chambers, MBBS, MD, Queensland Lung Transplant Service, Level 1, Administration Building, The Prince Charles Hospital, Rode Rd, Chermside, Queensland 4032, Australia. (daniel.chambers@health.qld.gov.au).

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