Haemoadsorption reduces the inflammatory response and improves blood flow during ex vivo renal perfusion in an experimental model

Abstract

BackgroundEx-vivo normothermic perfusion strategies are a promising new instrument in organ transplantation. The perfusion conditions are designed to be protective however the artificial environment can induce a local inflammatory response. The aim of this study was to determine the effect of incorporating a Cytosorb adsorber into an isolated kidney perfusion system.MethodsPorcine kidneys were subjected to 22 h of cold ischaemia then reperfused for 6 h on an ex vivo reperfusion circuit. Pairs of kidneys were randomised to either control (n = 5) or reperfusion with a Cytosorb adsorber (n = 5) integrated into the circuit. Tissue, blood and urine samples were taken for the measurement of inflammation and renal function.ResultsBaseline levels of cytokines (IL-6, TNFα, IL-8, IL-10, IL-1β, IL-1α) were similar between groups. Levels of IL-6 and IL-8 in the perfusate significantly increased during reperfusion in the control group but not in the Cytosorb group (P = 0.023, 0.049). Levels of the other cytokines were numerically lower in the Cytosorb group; however, this did not reach statistical significance. The mean renal blood flow (RBF) was significantly higher in the Cytosorb group (162 ± 53 vs. 120 ± 35 mL/min/100 g; P = 0.022). Perfusate levels of prostaglandin E2 were significantly lower in the Cytosorb group (642 ± 762 vs. 3258 ± 980 pg/mL; P = 0.0001). Levels of prostacyclin were significantly lower in the Cytosorb group at 1, 3 and 6 h of reperfusion (P = 0.008, 0.003, 0.0002). Levels of thromboxane were also significantly lower in the Cytosorb group throughout reperfusion (P = 0.005). Haemoadsorption had no effect on creatinine clearance (P = 0.109).ConclusionHaemoadsorption can reduce the inflammatory response and improve renal blood flow during perfusion. Nonetheless, in this model haemoadsorption had no influence on renal function and this may relate to the broad-spectrum action of the Cytosorb adsorber that also removes potentially important anti-inflammatory mediators.

Clinical Utility of Extracorporeal Cytokine Hemoadsorption Therapy: A Literature Review

“…IL-10 and IL-1RA are crucial for the maintenance of epithelial structural integrity and for reducing the inflammatory responses through NF-κB signaling [8,128]. Additionally, IL-1RA diminishes the expression of the intracellular adhesion molecule (ICAM)-1, decreasing the risk of excessive cellular adhesion and aggregation [128].…”

“…Their function is to reduce the overall production of proinflammatory cytokines and to restore homeostasis once an infection is eradicated [7,8]. Besides initiating the host response to infection, antigen-presenting cells also participate in feedback inhibition pathways by expressing IL-4 and IL-10, which mitigate further inflammatory responses by macrophages [4].…”

Kidney Perfusion as an Organ Quality Assessment Tool—Are We Counting Our Chickens Before They Have Hatched?

“…We know that inflammatory cytokines are released during kidney perfusion, although it is currently unclear what cytokines are detectable and whether these would be predictive of outcome. The use of a cytokine filter during 6 hours of normothermic perfusion of porcine kidneys reduced levels of interleukin-8 (neutrophil-attractant) and interleukin-6 (pro-inflammatory cytokine) when compared to control [138]. However, neither a difference in kidney function during normothermic perfusion could be noted nor were kidneys transplanted [138].…”

Emerging technologies in organ preservation, tissue engineering and regenerative medicine: a blessing or curse for transplantation?

“…This provides the unique potential to deliver treatment solely to grafts during ex vivo perfusion, bypassing complications that arise from systemic delivery in the recipient. Different approaches of ex vivo therapies have already been tested including cytokine absorption , addition of noble gas , as well as stem cell and gene therapies. Cytosorb absorber, a nonselective filter of cytokines and vasoactive substances, showed improvement in initial renal blood flow in the setting of porcine kidney preservation .…”

“…Different approaches of ex vivo therapies have already been tested including cytokine absorption , addition of noble gas , as well as stem cell and gene therapies. Cytosorb absorber, a nonselective filter of cytokines and vasoactive substances, showed improvement in initial renal blood flow in the setting of porcine kidney preservation . The application of 70% argon during MP displayed favorable results on renal blood flow; however, no measurable effects on other different outcome parameters were detected .…”