Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors

Abstract

Objective: To test the hypothesis that extracorporeal therapy with polymyxin B (PMX-B) may prevent Gram-negative sepsisinduced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors. Setting: Medical-Surgical Intensive Care Units. Patients and interventions: Sixteen patients with Gram-negative sepsis were randomized to receive standard care (Surviving Sepsis Campaign guidelines) or standard care plus extracorporeal therapy with PMX-B. Measurements and results: Cell viability, apoptosis, polarity, morphogenesis, and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups. Renal function was evaluated as SOFA and RIFLE scores, proteinuria, and tubular enzymes. A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells. SOFA and RIFLE scores, proteinuria, and urine tubular enzymes were all significantly reduced after PMX-B treatment. Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity. Conclusions: Extracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells. These data confirm the role of apoptosis in the development of sepsisrelated ARF.

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

“…The main objective of therapeutic apheresis is the removal of toxic substances, although the method can also be applied for immunomodulation. It was reported that the absorption of anandamide by polymyxin B might abolish the diverse negative effects of anandamide, such as hypotension, immunosuppression, and cytotoxicity,53 and that the reduction of serum cytokine levels54 or monocyte mRNA expression,55 and the proapoptotic activity of plasma56 from septic patients might contribute to the efficacy of hemoperfusion with PMX‐F. We previously reported that the expression of HLA‐DR surface antigen on monocytes is decreased in patients with septic shock, and that PMX‐F therapy is effective for increasing its expression 26.…”

Renal Cell Apoptosis and New Treatment Options in Sepsis-Induced Acute Kidney Injury

“…It seems likely that plasma separation techniques can prove to be beneficial in renal injury by removing the pro-apoptotic factors and cytokines. 20 Ghrelin shows a protective effect on kidneys by inhibiting pro-inflammatory cytokines, particularly TNF-α, in the circulation and in kidneys. Ghrelin may thus hold promise for managing endotoxemia-induced AKI.…”

Acute kidney injury in sepsis

“…Studies based on the importance of cytokines in this process have offered haemadsorption as a potential strategy to prevent the onset of AKI in sepsis [28]. Extracorporeal therapy with Polymixin B has been shown in some clinical studies to reduce pro-apoptotic factors leading to kidney injury and to reduce organ dysfunction in sepsis [29,30]. Adjunctive treatment with exogenous alkaline phosphatase is currently under investigation for its detoxifying potential [16].…”