title: Tailoring high-cut-off membranes and feasible application in sepsis-associated acute renal failure: in vitro studies.
abstract: BACKGROUND
  As removal of pro-inflammatory cytokines is limited in conventional diffusive or convective extracorporeal therapies, we studied in two polysulphone membranes with an industrial albumin sieving coefficient of 0.05 (Type A) and 0.13 (Type B) cytokine (IL-6, IL-8, IL-1beta, IL-1ra, TNF-alpha) and plasma protein (albumin, cystatin C, total proteins) permeability profiles. Based on the convective membrane permeability, we evaluated in vitro the dialytic modality that could provide an acceptable balance between high cytokine and low albumin clearances.
  
  
  METHODS
  Cytokine and plasma protein sieving coefficient (SC) and clearance were studied in (i) post-dilutional haemofiltration mode at 20% fixed ultrafiltration rate; (ii) haemodialysis mode (dialysate flow rate of 3 and 5 l/h); and (iii) haemodiafiltration mode (dialysate flow rate of 3 or 5 l/h with 0.5 l/h of ultrafiltrate).
  
  
  RESULTS
  In haemofiltration mode both Type A and Type B haemodialysers at QB 150 ml/min exhibited similar median SC nearly up to 1 for IL-1beta and IL-1ra, at about 0.6 for IL-6, 0.4 for IL-8 and 0.7 for TNF-alpha, with clearance values ranging from 15 to 30 ml/min. SC were independent of blood flow and were stable throughout the whole experiment. Albumin SC was higher in Type B than in Type A and rapidly decreased from 0.2 to 0.02 and from 0.5 to 0.04 within 3 h for haemodialyser Types A and B, respectively. Cytokine SC was lower in haemodialysis than in haemodiafiltration and haemofiltration mode, and by increasing dialysate flow from 3 up to 5 l/h in both haemodialysis and haemodiafiltration mode, SC for all tested cytokines decreased. However, at 5 l/h clearances were not different or were higher, since increased amounts of dialysate outlet compensated for the decreased SC. Albumin clearances in haemodialysis and haemodiafiltration mode after 360 min at 5 l/h were 0.81 and 0.91 ml/min, respectively.
  
  
  CONCLUSIONS
  Our studies show that a mixed convective and diffusive technique ensures high cytokine clearances with an acceptable loss of albumin.
authors.affiliation: Department of Medicine Area, Nephrology and Dialysis Unit, CTO Hospital, Turin 10126, Italy. filippo.mariano@poste.it
authors.forename: Filippo
authors.initials: F
authors.lastname: Mariano
authors.forename: Valentina
authors.initials: V
authors.lastname: Fonsato
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lanfranco
authors.forename: Robert
authors.initials: R
authors.lastname: Pohlmeier
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
authors.forename: Giorgio
authors.initials: G
authors.lastname: Triolo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.forename: Ciro
authors.initials: C
authors.lastname: Tetta
authors.forename: Jutta
authors.initials: J
authors.lastname: Passlick-Deetjen
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D004867:Equipment Design; D006440:Hemofiltration; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000097:blood; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D011108:Polymers; D006435:Renal Dialysis / Q000295:instrumentation*; D018805:Sepsis / Q000150:complications*; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha
chemical_list: D016207:Cytokines; D007378:Interleukins; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C017662:polysulfone P 1700