Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors.
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.
Cantaluppi
Vincenzo
V
Dipartimento di Medicina Interna, Centro Ricerca Medicina Sperimentale (CeRMS), Torino, Italy.
Assenzio
Barbara
B
Pasero
Daniela
D
Romanazzi
Giuseppe Mauriello
GM
Pacitti
Alfonso
A
Lanfranco
Giacomo
G
Puntorieri
Valeria
V
Martin
Erica L
EL
Mascia
Luciana
L
Monti
Gianpaola
G
Casella
Giampaolo
G
Segoloni
Giuseppe Paolo
GP
Camussi
Giovanni
G
Ranieri
V Marco
VM
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
D000900:Anti-Bacterial Agents; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases; D011112:Polymyxin B