Heparin-Binding Protein (HBP) : A Causative Marker and Potential Target for Heparin Treatment of Human Sepsis-Induced Acute Kidney Injury

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Fältnamn	Indikatorer	Metadata
000		04857naa a2200385 4500
001		oai:lup.lub.lu.se:09152aab-e760-4ea0-b373-689925b9899d
003		SwePub
008		170914s2017 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/09152aab-e760-4ea0-b373-689925b9899d2 URI
024	7	a https://doi.org/10.1097/SHK.00000000000008622 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Fisher, Janeu Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital,University of British Columbia4 aut0 (Swepub:lu)med-jfi
245	1 0	a Heparin-Binding Protein (HBP) : A Causative Marker and Potential Target for Heparin Treatment of Human Sepsis-Induced Acute Kidney Injury
264	1	c 2017
300		a 8 s.
520		a RATIONALE: Sepsis-induced acute kidney injury (AKI) is a common condition with high morbidity and mortality. Neutrophil-derived heparin-binding protein (HBP) induces vascular leakage and is a promising biomarker of sepsis-induced organ dysfunction. It remains unknown if HBP is prognostic of AKI in septic shock and if HBP could play a role in the pathophysiology of sepsis-induced AKI.OBJECTIVES: To determine the association of plasma HBP levels with development of AKI, investigate the role of HBP in the pathophysiology of sepsis-induced AKI, and test the effect of blocking HBP using heparin derivatives.METHODS: In 296 septic shock patients from the randomized multicenter Vasopressin and Septic Shock Trial (VASST) plasma HBP levels were associated with development of AKI and need for renal replacement therapy (RRT). Human renal tubular cells were exposed to recombinant HBP to evaluate inflammation and heparin derivatives were used to abrogate these effects. Finally, mice were exposed to HBP with and without heparin derivatives and the kidneys examined for signs of inflammation.FINDINGS: Plasma HBP levels were significantly higher in patients with AKI and those requiring RRT. HBP levels identified patients with moderate AKI with an area under curve (AUC) of 0.85. HBP increased IL-6 production in renal tubular epithelial cells. Different heparin derivatives abrogated the HBP-induced increased inflammatory response in vitro and in vivo.CONCLUSION: Elevated plasma HBP is associated with development of sepsis-induced AKI and HBP is involved in its pathophysiology. Our studies suggest that heparin(s) could be tested for efficacy and safety of prevention of sepsis-induced AKI.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng
700	1	a Russell, James A.u University of British Columbia4 aut
700	1	a Bentzer, Peteru Lund University,Lunds universitet,Anestesiologi och intensivvård,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Anesthesiology and Intensive Care,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,University of British Columbia,Helsingborg Hospital4 aut0 (Swepub:lu)mphy-pbe
700	1	a Parsons, Devynu University of British Columbia4 aut
700	1	a Secchia, Stefanou Lund University,Skåne University Hospital4 aut
700	1	a Mörgelin, Matthiasu Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)medk-mmn
700	1	a Walley, Keith R.u University of British Columbia4 aut
700	1	a Boyd, John H.u University of British Columbia4 aut
700	1	a Linder, Adamu Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Translationell Sepsisforskning,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Translational Sepsis research,Lund University Research Groups,University of British Columbia4 aut0 (Swepub:lu)infe-lad
710	2	a Infektionsmedicinb Sektion III4 org
773	0	t Shockg 48:3, s. 313-320q 48:3<313-320x 1540-0514
856	4	u http://dx.doi.org/10.1097/SHK.0000000000000862y FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/09152aab-e760-4ea0-b373-689925b9899d
856	4 8	u https://doi.org/10.1097/SHK.0000000000000862

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Av författaren/redakt...: Fisher, Jane; Russell, James A ...; Bentzer, Peter; Parsons, Devyn; Secchia, Stefano; Mörgelin, Matthi ...; visa fler...; Walley, Keith R.; Boyd, John H.; Linder, Adam; visa färre...

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