title: High cut-off dialysis in chronic haemodialysis patients.
abstract: BACKGROUND
  Haemodialysis patients suffer from chronic systemic inflammation and high incidence of cardiovascular disease. One cause for this may be the failure of diseased kidneys to eliminate immune mediators. Current haemodialysis treatment achieves insufficient elimination of proteins in the molecular weight range 15-45 kD. Thus, high cut-off dialysis might improve the inflammatory state.
  
  
  METHODS
  In this randomized crossover trial, 43 haemodialysis patients were treated for 3 weeks with high cut-off or high-flux dialysis. Inflammatory plasma mediators, monocyte subpopulation distribution and leucocyte gene expression were quantified.
  
  
  RESULTS
  High cut-off dialysis supplemented by a low-flux filter did not influence the primary end-point, expression density of CD162 on monocytes. Nevertheless, treatment reduced multiple immune mediators in plasma. Such reduction proved - at least for some markers - to be a sustained effect over the interdialytic interval. Thus, for example, soluble TNF-receptor 1 concentration predialysis was reduced from median 13·3 (IQR 8·9-17·2) to 9·7 (IQR 7·5-13·2) ng/mL with high cut-off while remaining constant with high-flux treatment. The expression profile of multiple proinflammatory genes in leucocytes was significantly dampened. Treatment was well tolerated although albumin losses in high cut-off dialysis would be prohibitive against long-term use.
  
  
  CONCLUSIONS
  The study shows for the first time that a dampening effect of high cut-off dialysis on systemic inflammation is achievable. Earlier studies had failed due to short study duration or insufficient dialysis efficacy. Removal of soluble mediators from the circulation influences cellular activation levels in leucocytes. Continued development of less albumin leaky membranes with similar cytokine elimination is justified.
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle, Halle, Germany.
authors.forename: Matthias
authors.identifier: http://orcid.org/0000-0003-2823-0847
authors.initials: M
authors.lastname: Girndt
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle, Halle, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Fiedler
authors.affiliation: Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.affiliation: NMI Technology Transfer GmbH, Reutlingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlak
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Storr
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Bohler
authors.affiliation: Institute for Chemistry, Food Chemistry, Martin-Luther-University Halle, Halle, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Glomb
authors.affiliation: Institute for Chemistry, Food Chemistry, Martin-Luther-University Halle, Halle, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Liehr
authors.affiliation: Institute for Chemistry, Food Chemistry, Martin-Luther-University Halle, Halle, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Henning
authors.affiliation: NMI Technology Transfer GmbH, Reutlingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Templin
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle, Halle, Germany.
authors.forename: Bogusz
authors.initials: B
authors.lastname: Trojanowicz
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle, Halle, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Ulrich
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Werner
authors.affiliation: Department of Nephrology and Internal Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zickler
authors.affiliation: Department of Nephrology and Internal Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schindler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D018592:Cross-Over Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000378:metabolism; D061214:Patient Safety; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: High cut-off membrane; haemodialysis; inflammation; monocytes; multiplex immunoassay