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A model of acute kidney injury in mice with cirrhosis and infection
Author(s) -
Carl Daniel E.,
Ghosh Siddhartha S.,
Gehr Todd W.B.,
Abbate Antonio,
Toldo Stefano,
Sanyal Arun J.
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13023
Subject(s) - ccl4 , medicine , cirrhosis , renal function , creatinine , acute kidney injury , carbon tetrachloride , gastroenterology , kidney , proteinuria , endocrinology , urology , pharmacology , chemistry , organic chemistry
Background & Aims Infectious acute kidney injury ( AKI ) is a life threatening complication of cirrhosis with limited therapeutic options. The aim of this study was to develop a model of infectious AKI in cirrhotic mice. Methods Cirrhosis was established by intragastric administration of carbon tetrachloride ( CC l 4 ). Systemic haemodynamics was assessed invasively while cardiac function was assessed by echocardiography. AKI was induced using varying doses of lipopolysaccharide ( LPS ) 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 + LPS , and (iii) mice treated with CC l 4 alone. Results Cirrhosis with increased cardiac output, decreased systemic vascular resistance, activation of renin–angiotensin–aldosterone axis developed after 12 weeks of CC l 4 administration. LPS injection produced a dose‐dependent 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 LPS injection produced a rise in creatinine (0.79 ± 0.27 mg/dl in CC l 4 + LPS compared to 0.45 ± 0.14 in CC l 4 alone, P < 0.05) and a decrease in UOP (0.86 ± 0.4 ml/16 h in CC l 4 + LPS compared to 1.70 ± 0.7 ml/16 h in CC l 4 mice, P < 0.05). UOP remained low in mice that died while it recovered over 48–72 h in those that recovered. Control mice treated with 2 mg/kg LPS did not experience AKI. Conclusions Cirrhotic CC l 4 treated mice develop functional AKI and mimic most of the features of infectious AKI following LPS injection.