Angiopoietin Balance in Septic Shock Patients With Acute Kidney Injury: Effects of Direct Hemoperfusion With Polymyxin B-Immobilized Fiber.

Acute kidney injury (AKI) occurs in approximately 50% of patients in septic shock, and mortality from septic AKI is extremely high. Angiopoietin levels may play a role in the pathogenesis of vascular permeability. It was reported that direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX) therapy ameliorates the angiopoietin balance in patients with sepsis. Although dysregulated angiopoietin balance in sepsis has been demonstrated, mechanisms underlying the development of AKI in sepsis have not been identified. We investigated angiopoietin levels in septic patients with/without AKI treated with DHP-PMX therapy. We used an enzyme-linked immunoassay to measure serum angiopoietin-1 and -2 levels in 38 septic shock patients treated with DHP-PMX. The renal function of all patients was normal for less than 3 months. Twenty-seven of the patients were diagnosed with AKI. The angiopoietin-1 level of the AKI group was significantly lower than that of the non-AKI group at the initiation of DHP-PMX therapy, but there was no significant difference between the two groups at the end of DHP-PMX therapy. In the AKI group with recovery, the mean angiopoietin-1 level at the end of DHP-PMX therapy was significantly elevated compared to the level before DHP-PMX therapy, and the mean angiopoietin-2 level at the end of DHP-PMX therapy was significantly decreased compared to the level before DHP-PMX therapy. These results suggest that angiopoietins may play a role in the pathogenesis of AKI and that DHP-PMX therapy may ameliorate the angiopoietin balance in AKI patients with sepsis.

Soluble vascular endothelial-cadherin levels in patients with sepsis treated with direct hemoperfusion with a polymyxin B-immobilized fiber column.

Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. Several molecules are investigated as associated factors with capillary permeability and vascular endothelial (VE)-cadherin internalization by vascular endothelial growth factor (VEGF)-induced signaling through VEGF receptors leads to increased vascular endothelial cell detachment and trans-endothelial permeability. We investigated serum soluble VE-cadherin levels in septic patients. An enzyme-linked immunoassay was used to measure serum soluble VE-cadherin levels in 47 septic patients treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The serum soluble VE-cadherin level of septic patients before PMX-DHP was 3424.1 ± 2033.0 ng/mL, which was significantly lower than that of the controls (5862.0 ± 1521.2 ng/mL; P < 0.0001). The time course of serum soluble VE-cadherin levels remained unchanged during PMX-DHP therapy. There was no significant difference in serum soluble VE-cadherin levels before PMX-DHP therapy between survivors and non-survivors, and there was no significant difference in those levels between the groups at any time after the initiation of PMX-DHP therapy. There was no correlation between soluble VE-cadherin levels and clinical data, except white blood cell count (r = -0.277, P = 0.0009). There was no correlation between soluble VE-cadherin levels and the levels of angiopoietin 1 and 2. In summary, the relationship between VE-cadherin and capillary permeability in sepsis could not be demonstrated. Soluble VE-cadherins are not reflected in the balance between intercellular junction plasticity and integrity, but VE-cadherin stabilization by its phosphorylation or internalization may be associated with capillary permeability.