BACKGROUND: Renal replacement therapies with high cut-off haemofilters are new approaches in the adjuvant therapy of sepsis. We analysed the cytokine elimination capacity of a newly developed polyflux high cut-off haemofilter. Different renal replacement therapies are compared and tested for their clinical feasibility. METHODS: Blood from healthy volunteers (n=15) was incubated for 4 h with 1 mg of endotoxin and then circulated through a closed extracorporeal circuit. A newly developed polyflux haemofilter (P2SX) was used. Haemofiltration, haemodialysis and albumin dialysis were tested. IL-1ra (17 kDa), interleukin-6 (IL-6) (28 kDa), tumour necrosis factor alpha (TNF-alpha) (51 kDa), albumin (64 kDa), creatinkinase (CK) (80 kDa) and IgG (140 kDa) were measured in blood and filtrates prior to the initiation and after 5 min, 1, 2 and 4 h. RESULTS: Haemofiltration was superior to haemodialysis in the clearance capacity of all substances when applied in the 1 l/h ultrafiltration mode. Increasing the ultrafiltration rate/dialysate flow from 1 to 3 l/h led to a significant increase in cytokine clearances (P<0.001). At 3 l/h the differences between haemofiltration and haemodialysis vanished and both techniques achieved comparable cytokine clearances. Median clearance values ranged between 25 and 54 ml/min for interleukin-1 receptor antagonist (IL-1ra), 23 and 42 ml/min for IL-6 and 15 and 28 ml/min for TNF-alpha. Albumin loss was highest in the haemofiltration group with albumin clearances ranging between 7 and 13 ml/min. Using diffusion instead of convection significantly reduced the loss of albumin (P<0.01 for 1 l/h, P<0.05 for 3 l/h). Albumin dialysis was able to completely inhibit albumin loss but cytokine clearance capacity was limited. CONCLUSIONS: High cut-off haemofilters achieve high clearances for inflammatory IL-6 and TNF-alpha. Due to the high protein loss in haemofiltration, dialysis in combination with balanced protein substitution seems to be a suitable approach for clinical trials.
BACKGROUND: Renal replacement therapies with high cut-off haemofilters are new approaches in the adjuvant therapy of sepsis. We analysed the cytokine elimination capacity of a newly developed polyflux high cut-off haemofilter. Different renal replacement therapies are compared and tested for their clinical feasibility. METHODS: Blood from healthy volunteers (n=15) was incubated for 4 h with 1 mg of endotoxin and then circulated through a closed extracorporeal circuit. A newly developed polyflux haemofilter (P2SX) was used. Haemofiltration, haemodialysis and albumin dialysis were tested. IL-1ra (17 kDa), interleukin-6 (IL-6) (28 kDa), tumour necrosis factor alpha (TNF-alpha) (51 kDa), albumin (64 kDa), creatinkinase (CK) (80 kDa) and IgG (140 kDa) were measured in blood and filtrates prior to the initiation and after 5 min, 1, 2 and 4 h. RESULTS: Haemofiltration was superior to haemodialysis in the clearance capacity of all substances when applied in the 1 l/h ultrafiltration mode. Increasing the ultrafiltration rate/dialysate flow from 1 to 3 l/h led to a significant increase in cytokine clearances (P<0.001). At 3 l/h the differences between haemofiltration and haemodialysis vanished and both techniques achieved comparable cytokine clearances. Median clearance values ranged between 25 and 54 ml/min for interleukin-1 receptor antagonist (IL-1ra), 23 and 42 ml/min for IL-6 and 15 and 28 ml/min for TNF-alpha. Albumin loss was highest in the haemofiltration group with albumin clearances ranging between 7 and 13 ml/min. Using diffusion instead of convection significantly reduced the loss of albumin (P<0.01 for 1 l/h, P<0.05 for 3 l/h). Albumin dialysis was able to completely inhibit albumin loss but cytokine clearance capacity was limited. CONCLUSIONS: High cut-off haemofilters achieve high clearances for inflammatory IL-6 and TNF-alpha. Due to the high protein loss in haemofiltration, dialysis in combination with balanced protein substitution seems to be a suitable approach for clinical trials.
Authors: Rinaldo Bellomo; Claudio Ronco; Ravindra L Mehta; Pierre Asfar; Julie Boisramé-Helms; Michael Darmon; Jean-Luc Diehl; Jacques Duranteau; Eric A J Hoste; Joannes-Boyau Olivier; Matthieu Legrand; Nicolas Lerolle; Manu L N G Malbrain; Johan Mårtensson; Heleen M Oudemans-van Straaten; Jean-Jacques Parienti; Didier Payen; Sophie Perinel; Esther Peters; Peter Pickkers; Eric Rondeau; Miet Schetz; Christophe Vinsonneau; Julia Wendon; Ling Zhang; Pierre-François Laterre Journal: Ann Intensive Care Date: 2017-05-04 Impact factor: 6.925
Authors: Karla C L Lee; Luisa A Baker; Giacomo Stanzani; Hatim Alibhai; Yu Mei Chang; Carolina Jimenez Palacios; Pamela J Leckie; Paola Giordano; Simon L Priestnall; Daniel J Antoine; Rosalind E Jenkins; Christopher E Goldring; B Kevin Park; Fausto Andreola; Banwari Agarwal; Rajeshwar P Mookerjee; Nathan A Davies; Rajiv Jalan Journal: J Hepatol Date: 2015-05-01 Impact factor: 25.083
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Authors: Gianluca Villa; Cosimo Chelazzi; Elena Morettini; Lucia Zamidei; Serafina Valente; A Lucia Caldini; Giovanni Zagli; A Raffaele De Gaudio; Stefano Romagnoli Journal: PLoS One Date: 2017-02-16 Impact factor: 3.240
Authors: L Kleeberg; S Morgera; C Jakob; B Hocher; M Schneider; H Peters; S Rötzer; C Müller; M Kaiser; C Fleissner; U Heider; H-H Neumayer; O Sezer Journal: Eur J Med Res Date: 2009 Impact factor: 2.175