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The aim of this study was to develop a model of infectious <jats:styled-content style=\"fixed-case\">AKI<\/jats:styled-content> in cirrhotic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cirrhosis was established by intragastric administration of carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>). Systemic haemodynamics was assessed invasively while cardiac function was assessed by echocardiography. <jats:styled-content style=\"fixed-case\">AKI<\/jats:styled-content> was induced using varying doses of lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) titrated to produce 50% lethality. Renal function was assessed from serum creatinine and urine output (UOP). Renal injury was evaluated by urinalysis (proteinuria and casts) and renal histology. These mice were compared to: (i) normal mice, (ii) normal mice + <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>, and (iii) mice treated with <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cirrhosis with increased cardiac output, decreased systemic vascular resistance, activation of renin\u2013angiotensin\u2013aldosterone axis developed after 12 weeks of <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> administration. <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> injection produced a dose\u2010dependent increase in mortality (33% at 2 mg\/kg vs. 80% at 6 mg\/kg) without urine (casts or proteinuria) or histological evidence of tubular injury. 2 mg\/kg <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> injection produced a rise in creatinine (0.79 \u00b1 0.27 mg\/dl in <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>+<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> compared to 0.45 \u00b1 0.14 in <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> alone, <jats:italic>P<\/jats:italic> &lt; 0.05) and a decrease in UOP (0.86 \u00b1 0.4 ml\/16 h in <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> + <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> compared to 1.70 \u00b1 0.7 ml\/16 h in <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> mice, <jats:italic>P<\/jats:italic> &lt; 0.05). UOP remained low in mice that died while it recovered over 48\u201372 h in those that recovered. Control mice treated with 2 mg\/kg <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> did not experience AKI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cirrhotic <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> treated mice develop functional <jats:styled-content style=\"fixed-case\">AKI<\/jats:styled-content> and mimic most of the features of infectious <jats:styled-content style=\"fixed-case\">AKI<\/jats:styled-content> following <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> injection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13023","type":"journal-article","created":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T14:22:39Z","timestamp":1447942959000},"page":"865-873","source":"Crossref","is-referenced-by-count":19,"title":["A model of acute kidney injury in mice with cirrhosis and infection"],"prefix":"10.1111","volume":"36","author":[{"given":"Daniel 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