title: TNF-alpha elimination with high cut-off haemofilters: a feasible clinical modality for septic patients?
abstract: 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.affiliation: Department of Nephrology, Charité, Humboldt University of Berlin, Germany. stanislao.morgera@charite.de
authors.forename: Stanislao
authors.initials: S
authors.lastname: Morgera
authors.forename: Daniela
authors.initials: D
authors.lastname: Klonower
authors.forename: Jens
authors.initials: J
authors.lastname: Rocktäschel
authors.forename: Michael
authors.initials: M
authors.lastname: Haase
authors.forename: Friedrich
authors.initials: F
authors.lastname: Priem
authors.forename: Sabine
authors.initials: S
authors.lastname: Ziemer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wegner
authors.forename: Hermann
authors.initials: H
authors.lastname: Göhl
authors.forename: Hans-H
authors.initials: HH
authors.lastname: Neumayer
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000628:therapy* / Q000652:urine*; D000328:Adult; D000970:Antineoplastic Agents / Q000652:urine*; D016207:Cytokines / Q000652:urine*; D004867:Equipment Design; D005240:Feasibility Studies; D006440:Hemofiltration / Q000295:instrumentation*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000652:urine*; D012016:Reference Values; D006435:Renal Dialysis / Q000295:instrumentation*; D018805:Sepsis / Q000150:complications / Q000628:therapy* / Q000652:urine*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000652:urine*
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha