The Effects of Polymyxin-B Protects on Sepsis Induced Kidney Dysfunction: a Randomized Clinical Trial

The Effects of Polymyxin-B Protects on Sepsis Induced Kidney Dysfunction: a Randomized Clinical Trial

Aim of the study is to verify whether Polymyxin-B hemoperfusion protects from renal dysfunction in patients with severe sepsis from gram negative infection.

Acute renal failure (ARF) is a frequent complication in sepsis, in nearly to 50% of the cases, and the mortality rate is higher, compare to patients with ARF alone (70% vs 45%). Clinical and experimental studies demonstrated the key role of apoptosis, or programmed cell death, in the induction of tubular and glomerular injury in the course of sepsis. Indeed, it has been shown that inflammatory cytokines and lipopolysaccharide (LPS) cause renal tubular cell apoptosis via Fas- and caspase-mediated pathways. In addition, LPS is able to alter the normal expression pattern of sodium, urea and glucose renal transporters and to modulate tubular polarity by changing the expression of tight junction proteins with consequent back-leakage of tubular fluid in the interstitial spaces and enhancement of the inflammatory process. Therefore a novel extracorporeal therapy to remove circulating LPS, using the Polymyxin-B fiber (PMX-B) cartridge was developed. The PMX-B cartridge is an extracorporeal hemoperfusion device and consists of a polystyrene-based, fibrous adsorbent on which the polymyxin B antibiotic is covalently immobilized as a ligand to adsorb endotoxin. Aim of this study is to verify whether the removal of LPS, using the PMX-B hemoperfusion system, protects from acute renal failure, reduces the need for Renal Replacement Therapy (RRT) and consequently improves the outcome in severe sepsis from gram negative infection.

acute renal failure, lipopolysaccharide, tubular apoptosis, Polymyxin-B fiber, Severe sepsis from gram negative infection

The Reduction of the Number of Apoptotic Cells, Stimulated With Plasma Derives From Septic Patients With Gram Negative Infection, Treated With PMX-B Hemoperfusion, on Immortalized Tubular and Glomerular Cell Cultures.

Inclusion Criteria: Endotoxemia associated to severe sepsis Exclusion Criteria: Age < 18 years old Organ transplantation Hemorrhagic shock Thrombophilia Chronic renal failure Cardiogenic shock APACHE II score > 30 Lack of consent

Cantaluppi V, Assenzio B, Pasero D, Romanazzi GM, Pacitti A, Lanfranco G, Puntorieri V, Martin EL, Mascia L, Monti G, Casella G, Segoloni GP, Camussi G, Ranieri VM. Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors. Intensive Care Med. 2008 Sep;34(9):1638-45. doi: 10.1007/s00134-008-1124-6. Epub 2008 May 8.