Renal inflammatory changes in acute hepatic failure-associated acute kidney injury.

BACKGROUND/AIMS: 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.

The clinical significance of antibody to vascular endothelial cells after renal transplantation.

Vascular endothelial cells (ECs) are considered to be a primary target for injury in allograft rejection. However, the relationship between serum antibody activity to ECs and rejection episodes has not been examined extensively in renal transplantation. Twenty-two renal transplant recipients were included in this study. Serum antibody activity to vascular endothelial cells (AECA) was measured using a cellular enzyme-linked immunosorbent assay (ELISA) in which human umbilical vein endothelial cells (HUVEC) and human glomerular endothelial cells (HGEC) were preincubated with TNF-alpha used as target cells. Serum samples were obtained just before transplantation and once a week during the immediate 1-3-month post-transplantation period. There was a significant correlation between the presence of AECA against HGEC and rejection episodes (P < 0.05). Patients with multi-episodes of rejection showed significantly higher frequencies of AECA than patients with mono-episodic rejection (P < 0.0005). It should be noted that patients suffering from multi-episodes of rejection revealed higher AECA titres before transplantation. These findings imply that the HGEC-ELISA could be used as a prospective, informative test to identify patients with a higher risk of acute rejection in renal transplantation.