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

Abstract

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.

Plasma proteomic characterization of the development of acute kidney injury in early sepsis patients

“…Further, an activated thromboxane A2 pathway causes platelet adhesion, capillary thrombosis and mediates vasoconstriction, decreasing kidney blood flow and function 38 – 40 . These findings are in line with other studies reporting the role of endothelial dysfunction in the development of sepsis-AKI 41 , 42 , 43 . Together, plasma proteomic profile of sepsis patients strongly suggest that endothelium dysfunction precedes development of acute kidney injury, suggesting that an endothelium protective strategy early in sepsis may protect from the development of sepsis-AKI.…”

Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment

“…92 Table 1 summarizes some biomarkers studied in S-AKI. [93][94][95][96][97][98][99][100][101][102][103][104][105][106][107] Neutrophil gelatinase-associated lipocalin (NGAL) has been extensively investigated in various AKI phenotypes. NGAL is released by activated neutrophils and various epithelial cells including renal TECs.…”

Polymyxin B hemoperfusion as a feasible therapy after source control in abdominal septic shock

“…In addition, one of the most common complications of septic shock is acute kidney injury (AKI) and it occurs in more than 20% of patients with sepsis that is related to higher mortality rate[28]. Ebihara et al[29] suggested that PMX-HP restored the angiopoietin-1 levels and diminished the levels of angiopoietin-2 in septic AKI, thereby preventing the apoptosis of renal tubular cells resulting in a protective effect against AKI[19]. Our results demonstrated a dramatic decrease in renal SOFA score, and considering the high mortality of septic AKI, authors expect that the removal of endotoxin or cytokines might protect the renal function in abdominal septic shock.…”