title: Renal inflammatory changes in acute hepatic failure-associated acute kidney injury.
abstract: OBJECTIVE
  Acute 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.
  
  
  METHODS
  We examined the mechanisms of AHF-associated AKI, which is characterized by AKI in AHF and hyperbilirubinemia, following DA-to-Lewis rat liver transplantation.
  
  
  RESULTS
  During 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.
  
  
  CONCLUSIONS
  AHF-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.
authors.affiliation: Department of Pathology (Analytic Human Pathology), Nippon Medical School, Tokyo, Japan. ashimizu@nms.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Masuda
authors.forename: Ayako
authors.initials: A
authors.lastname: Sato
authors.forename: Honglan
authors.initials: H
authors.lastname: Piao
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kunugi
authors.forename: Mikiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Mika
authors.initials: M
authors.lastname: Terasaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagasaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Terasaki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ohashi
authors.forename: Testuo
authors.initials: T
authors.lastname: Morioka
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D007249:Inflammation; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D017114:Liver Failure, Acute / Q000150:complications*; D008833:Microcirculation; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D014185:Transplantation, Isogeneic