title: 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 sepsis-induced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors.
  
  
  METHODS
  Medical-Surgical Intensive Care Units.
  
  
  METHODS
  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.
  
  
  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 sepsis-related ARF.
authors.affiliation: Dipartimento di Medicina Interna, Centro Ricerca Medicina Sperimentale (CeRMS), Torino, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cantaluppi
authors.forename: Barbara
authors.initials: B
authors.lastname: Assenzio
authors.forename: Daniela
authors.initials: D
authors.lastname: Pasero
authors.forename: Giuseppe Mauriello
authors.initials: GM
authors.lastname: Romanazzi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pacitti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lanfranco
authors.forename: Valeria
authors.initials: V
authors.lastname: Puntorieri
authors.forename: Erica L
authors.initials: EL
authors.lastname: Martin
authors.forename: Luciana
authors.initials: L
authors.lastname: Mascia
authors.forename: Gianpaola
authors.initials: G
authors.lastname: Monti
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Casella
authors.forename: Giuseppe Paolo
authors.initials: GP
authors.lastname: Segoloni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.forename: V Marco
authors.initials: VM
authors.lastname: Ranieri
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D007684:Kidney Tubules / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011112:Polymyxin B / Q000008:administration & dosage / Q000627:therapeutic use*; D018805:Sepsis / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases; D011112:Polymyxin B