Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors.

Area of Science:

• Nephrology
• Critical Care Medicine
• Pharmacology

Background:

• Gram-negative sepsis frequently leads to acute renal failure (ARF).
• Apoptosis, or programmed cell death, is implicated in the pathogenesis of sepsis-induced ARF.
• Circulating proapoptotic factors in sepsis plasma may contribute to renal injury.

Purpose of the Study:

• To investigate whether extracorporeal polymyxin B (PMX-B) therapy can prevent Gram-negative sepsis-induced ARF.
• To determine if PMX-B therapy reduces the activity of proapoptotic circulating factors in septic patients.

Main Methods:

• A randomized controlled trial was conducted in medical-surgical intensive care units.
• Sixteen patients with Gram-negative sepsis received either standard care or standard care plus PMX-B therapy.
• In vitro studies assessed the effects of patient plasma on cultured renal cells (tubular cells and podocytes).
• Renal function was evaluated using SOFA and RIFLE scores, proteinuria, and tubular enzymes.

Main Results:

• PMX-B treatment significantly decreased plasma-induced proapoptotic activity in cultured renal cells.
• Patients treated with PMX-B showed significant improvements in SOFA and RIFLE scores, reduced proteinuria, and lower levels of urine tubular enzymes.
• PMX-B therapy abrogated plasma-induced loss of cell polarity and permeability, preserving key molecules for renal integrity.

Conclusions:

• Extracorporeal PMX-B therapy effectively reduces the proapoptotic activity of plasma from septic patients on renal cells.
• These findings reinforce the critical role of apoptosis in the development of sepsis-related ARF.
• PMX-B therapy shows promise in preventing or mitigating acute kidney injury during Gram-negative sepsis.