• Akira Shimizu, Eiichi Ishii, Yukinari Masuda, Ayako Sato, Honglan Piao, Shinobu Kunugi, Mikiko Takahashi, Mika Terasaki, Shinya Nagasaka, Yasuhiro Terasaki, Ryuji Ohashi, Testuo Morioka, and Yuh Fukuda.
• Department of Pathology (Analytic Human Pathology), Nippon Medical School, Tokyo, Japan. ashimizu@nms.ac.jp
• Am. J. Nephrol. 2013 Jan 1; 37 (4): 378-88.

Background/AimsAcute kidney injury (AKI) is a common complication in advanced liver dysfunction. Our aim is to clarify the mechanisms of acute hepatic failure (AHF)-associated AKI.MethodsWe examined the mechanisms of AHF-associated AKI, which is characterized by AKI in AHF and hyperbilirubinemia, following DA-to-Lewis rat liver transplantation.ResultsDuring the progression of AHF and hyperbilirubinemia in liver graft rejection, AHF-associated AKI gradually developed by day 11. Degeneration and apoptotic cells were apparent in tubular epithelial cells with bile pigment accumulation and mitochondrial degeneration. Injury of peritubular capillaries (PTCs) was also noted with apoptotic endothelial cells, decreased expression of endothelial nitric oxide synthase, accumulation of α-smooth muscle actin+ pericytes and/or myofibroblasts, and inflammation. Angiogenic factors including vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in the cortex were decreased on day 11. In addition, a marked reduction in the velocity of red blood cells in PTCs was evident in vivo.ConclusionsAHF-associated AKI seems to be mediated by renal tubular epithelial cell injury with bile pigment accumulation, impaired microcirculation caused by PTC endothelial cell injury with depletion of endothelial nitric oxide synthase and angiogenic factors, and by a decrease in RBC velocity and renal inflammation. Multiple mechanisms including tubular and PTC injuries and renal inflammation may be involved in the development of AHF-associated AKI.Copyright © 2013 S. Karger AG, Basel.

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