title: Protective effect of resin adsorption on septic plasma-induced tubular injury.
abstract: BACKGROUND
  A pro-apoptotic effect of circulating mediators on renal tubular epithelial cells has been involved in the pathogenesis of sepsis-associated acute kidney injury (AKI). Adsorption techniques have been showed to efficiently remove inflammatory cytokines from plasma. The aim of this study was to evaluate the efficiency of the hydrophobic resin Amberchrom CG161 M to adsorb from septic plasma soluble mediators involved in tubular injury.
  
  
  METHODS
  We enrolled in the study 10 critically ill patients with sepsis-associated AKI and we evaluated the effects of their plasma on granulocyte adhesion, apoptosis and functional alterations of cultured human kidney tubular epithelial cells. We established an in vitro model of plasma adsorption and we studied the protective effect of unselective removal of soluble mediators by the Amberchrom CG161 M resin on septic plasma-induced tubular cell injury.
  
  
  RESULTS
  Plasma from septic patients induced granulocyte adhesion, apoptosis and altered polarity in tubular cells. Plasma adsorption significantly decreased these effects and abated the concentrations of several soluble mediators. The inhibition of granulocyte adhesion to tubular cells was associated with the down-regulation of ICAM-1 and CD40. Resin adsorption inhibited tubular cell apoptosis induced by septic plasma by down-regulating the activation of caspase-3, 8, 9 and of Fas/death receptor-mediated signalling pathways. The alteration of cell polarity, morphogenesis, protein reabsorption and the down-regulation of the tight junction molecule ZO-1, of the sodium transporter NHE3, of the glucose transporter GLUT-2 and of the endocytic receptor megalin all induced by septic plasma were significantly reduced by resin adsorption.
  
  
  CONCLUSIONS
  Septic plasma induced a direct injury of tubular cells by favouring granulocyte adhesion, by inducing cell apoptosis and by altering cell polarity and function. All these biological effects are related to the presence of circulating inflammatory mediators that can be efficiently removed by resin adsorption with a consequent limitation of tubular cell injury.
authors.affiliation: Center for Experimental Medical Research (CeRMS), University of Torino, Via Santena 5, Torino 10126, Italy. vincenzo.cantaluppi@unito.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cantaluppi
authors.forename: Viktoria
authors.initials: V
authors.lastname: Weber
authors.forename: Carola
authors.initials: C
authors.lastname: Lauritano
authors.forename: Federico
authors.initials: F
authors.lastname: Figliolini
authors.forename: Silvia
authors.initials: S
authors.lastname: Beltramo
authors.forename: Luigi
authors.initials: L
authors.lastname: Biancone
authors.forename: Massimo
authors.initials: M
authors.lastname: De Cal
authors.forename: Dinna
authors.initials: D
authors.lastname: Cruz
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
authors.forename: Giuseppe Paolo
authors.initials: GP
authors.lastname: Segoloni
authors.forename: Ciro
authors.initials: C
authors.lastname: Tetta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
mesh_terms: D000327:Adsorption; D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000097:blood / Q000302:isolation & purification*; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011108:Polymers / Q000494:pharmacology*; D018805:Sepsis / Q000097:blood* / Q000150:complications
chemical_list: C552102:Amberchrom CG161 M; D016207:Cytokines; D018836:Inflammation Mediators; D011108:Polymers