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Evaluation of the effect of hydroxyethyl starch on renal tubular epithelial cells in sepsis

English title Evaluation of the effect of hydroxyethyl starch on renal tubular epithelial cells in sepsis
Applicant Beck Schimmer Beatrice
Number 122305
Funding scheme Project funding (Div. I-III)
Research institution Institut für Anästhesiologie Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Clinical Pathophysiology
Start/End 01.10.2008 - 30.09.2011
Approved amount 331'000.00
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All Disciplines (2)

Discipline
Clinical Pathophysiology
Physiology : other topics

Keywords (10)

colloids; hydroxyethyl starch; sepsis; septic shock; volume therapy; acute renal failure; kidney proximal tubular cells; inflammation; cristalloids; tubular epithelial cells

Lay Summary (English)

Lead
Lay summary
Acute renal failure is a frequent complication of sepsis, a severe whole-body inflammatory state. The colloid hydroxyethyl starch (HES) is widely used in the treatment of such patients to restore their fluid volume. However, the effect of HES on renal function during sepsis remains controversial. This SNF projects aims at the evaluation of the effect of the colloid HES on kidneys during sepsis.In a first approach, a renal cell model of tumor necrosis factor-alpha (TNF-alpha)- stimulated human proximal tubular epithelial cells (kidney cells) was established to assess possible effects of HES 130 and HES 200 on these activated cells. HES 130 and HES 200 differ from each other regarding their molecular size.Cells were stimulated with TNF-alpha in the presence or absence of HES 130 or 200. After 4, 10, and 18 h of incubation monocyte chemoattractant protein-1 (MCP-1), a key chemoattractant for neutrophils and macrophages, was determined. In addition, viability- and cytotoxicity assays were performed.MCP-1 expression was doubled upon TNF-alpha exposure. In the presence of 2% and 4% HES 200 over a stimulation time period of 10 h and 18 h, MCP-1 concentration was decreased between 26% and 56% (p< 0.05). No differences between the TNF-alpha and TNF-alpha/HES 130 group was observed. TNF-alpha stimulation resulted in a significant decrease of viability by 53% - 63%, while viability decreased by only 32% - 40% in co-incubation with HES 130 (p< 0.005), and remained even less affected by TNF-alpha in the presence of HES 200 (p< 0.001). TNF-alpha-induced cell death rate was attenuated in the presence of HES 200 (p< 0.05).These data show that both HES products modulate renal cell injury upon inflammatory stimulation. The effect was more pronounced in the HES 200 group compared to HES 130, suggesting a possible biological difference between both HES types.Further studies are planned to evaluate the problem of fluid application in patients with sepsis regarding kidney function. This is an important aspect as certain types of fluids could further deteriorate kidney function. Beside harming the patient this would also significantly increase the costs with the performance of hemodialysis, which is correlated with additional risks for the patient.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Inflammatory kidney and liver tissue response to different hydroxyethylstarch (HES) preparations in a rat model of early sepsis
Schimmer Ralph C, Urner Martin, Voigtsberger Stefanie, Booy Christa, Roth Z'Graggen Birgit, Beck-Schimmer Beatrice, Schläpfer Martin (2016), Inflammatory kidney and liver tissue response to different hydroxyethylstarch (HES) preparations in a rat model of early sepsis, in PlosOne, 11, e0151903.
Propofol increases morbidity and mortality in a rat model of sepsis
Schläpfer Martin, Piegeler Tobias, Dull Randy O, Schwartz David E, Mao Mao, Bonini Marcelo G, Roth Z'Graggen Birgit, Beck-Schimmer Beatrice, Minshall Richard D (2015), Propofol increases morbidity and mortality in a rat model of sepsis, in Critical Care, 19, 45.
Modulation of early inflammatory response by different balanced and non-balanced colloids and crystalloids in a rodent model of endotoxemia
Voigtsberger Stefanie, Urner Martin, Hasler Melanie, Roth Z'Graggen Birgit, Booy Christa, Spahn Donat R, Beck-Schimmer B (2014), Modulation of early inflammatory response by different balanced and non-balanced colloids and crystalloids in a rodent model of endotoxemia, in PlosOne, 9, e93863.
Effect of hydroxyethyl starches (HES 130/0.42 and HES 200/0.5) on activated renal tubular epithelial cells
Wittlinger Moritz (2010), Effect of hydroxyethyl starches (HES 130/0.42 and HES 200/0.5) on activated renal tubular epithelial cells, in Anesth Analg, 110(2), 531-540.

Awards

Title Year
University of Zurich Semester Award for Doctoral Thesis of Moritz Wittlinger

Associated projects

Number Title Start Funding scheme
109558 Acute lung injury: key role of the respiratory epithelial compartment 01.10.2005 Project funding (Div. I-III)

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