Research
Protective effect of resin adsorption on septic plasma-induced tubular injury
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* Corresponding author: Giovanni Camussi giovanni.camussi@unito.it
1 Center for Experimental Medical Research (CeRMS), University of Torino, Via Santena 5, Torino 10126, Italy
2 Nephrology, Dialysis and Renal Transplantation Unit, Department of Internal Medicine, University of Torino, Corso Dogliotti 14, 10126, Italy
3 Department for Clinical Medicine and Biotechnology, Center for Biomedical Technology, Danube University Krems, Dr. Karl Dorrek Street 30, Krems, A-3500, Austria
4 Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Viale Rodolfi 37, Vicenza, 36100, Italy
5 Fresenius Medical Care, Daimlerstrasse 15, Bad Homburg, D-61352, Germany
6 Cattedra di Nefrologia, Dipartimento di Medicina Interna, Ospedale Maggiore S. Giovanni Battista, Corso Dogliotti 14, 10126, Torino, Italy
Critical Care 2010, 14:R4 doi:10.1186/cc8835
Published: 11 January 2010Abstract
Introduction
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.