OBJECTIVE Hepatorenal syndrome-induced acute kidney injury (AKI) comprises AKI and liver cirrhosis (LC) and is a risk factor for poor prognoses of patients with LC. Decreased a disintegrin-like metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) activity and increased von Willebrand factor (vWF) antigen levels are associated with LC progression and portal hypertension. We investigated the role of the ADAMTS13-vWF axis in AKI using an LC mouse model. METHODS Wild-type and ADAMTS13-deficient (Adamts13-/-) 129+Ter/Sv mice comprised the negative control and AKI groups. AKI was induced by intraperitoneal carbon tetrachloride, a single injection of a double dose of carbon tetrachloride, and lipopolysaccharide administration. Wild-type and vWF-deficient C57/B6J mice comprised a secondary animal model. Effects of ADAMTS13 alterations on liver and kidney injuries, and the role of vWF in AKI in the cirrhotic mouse model were analyzed. RESULTS AKI groups of wild-type and Adamts13-/- mice showed increased serum aspartate aminotransferase/alanine aminotransferase and blood urea nitrogen/creatinine levels. Significantly greater changes in Adamts13-/- mice were observed. Blood flow in the liver and kidney was significantly decreased in the AKI group of Adamts13-/- mice. The AKI group of Adamts13-/- mice also demonstrated inflammatory changes, including increased F4/80-positive cells and renal injury markers in the kidney. Oxidative stress markers were increased in Adamts13-/- mice after AKI induction. Conversely, vWF-deficient mice were protected from liver and kidney damage, and showed reduced tissue blood flow, inflammation, and oxidative stress responses. CONCLUSIONS An imbalanced ADAMTS13-vWF axis may play a critical role in AKI progression with LC.