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Sequential analysis of a panel of biomarkers and pathologic findings in a resuscitated rat model of sepsis and recovery

Arulkumaran, N; Sixma, ML; Jentho, E; Ceravola, E; Bass, PS; Kellum, JA; Unwin, RJ; ... Singer, M; + view all (2017) Sequential analysis of a panel of biomarkers and pathologic findings in a resuscitated rat model of sepsis and recovery. Critical Care Medicine , 45 (8) e821-e830. 10.1097/CCM.0000000000002381. Green open access

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Abstract

OBJECTIVES: To characterize the temporal pattern of a panel of blood and urinary biomarkers in an animal model of fecal peritonitis and recovery. DESIGN: Prospective observational animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: A fluid-resuscitated, long-term (3 d) rat model of sepsis (fecal peritonitis) and recovery was used to understand the temporal association of sepsis biomarkers in relation to systemic hemodynamics, inflammation, and renal function. At predefined time points (3, 6, 12, 24, 48, 72 hr), animals (≥ 6 per group) underwent echocardiography, blood and urine sampling, and had kidneys taken for histological analysis. Comparison was made against sham-operated controls and naïve animals. MEASUREMENTS AND MAIN RESULTS: The systemic proinflammatory response was maximal at 6 hours, corresponding with the nadir of stroke volume. Serum creatinine peaked late (24 hr), when clinical recovery was imminent. Histological evidence of tubular injury and cell death was minimal. After a recovery period, all biomarkers returned to levels approaching those observed in sham animals. Apart from urine clusterin and interleukin-18, all other urinary biomarkers were elevated at earlier time points compared with serum creatinine. Urine neutrophil gelatinase-associated lipocalin was the most sensitive marker among those studied, rising from 3 hours. While serum creatinine fell at 12 hours, serum cystatin C increased, suggestive of decreased creatinine production. CONCLUSIONS: Novel information is reported on the temporal profile of a panel of renal biomarkers in sepsis in the context of systemic and renal inflammation and recovery. Insight into the pathophysiology of acute kidney injury is gleaned from the temporal change markers of renal injury (urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, calbindin), followed by a marker of cell cycle arrest (urine insulin-like growth factor-binding protein 7) and, finally, by functional markers of filtration (serum creatinine and cystatin C). These clinically relevant findings should have significant influence on future clinical testing.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Type: Article
Title: Sequential analysis of a panel of biomarkers and pathologic findings in a resuscitated rat model of sepsis and recovery
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/CCM.0000000000002381
Publisher version: http://doi.org/10.1097/CCM.0000000000002381
Language: English
Additional information: Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: acute kidney injury; animal model; biomarkers; sepsis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1555432
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