title: Medium Cut-Off (MCO) Membranes Reduce Inflammation in Chronic Dialysis Patients-A Randomized Controlled Clinical Trial.
abstract: BACKGROUND
  To increase the removal of middle-sized uremic toxins a new membrane with enhanced permeability and selectivity, called Medium Cut-Off membrane (MCO-Ci) has been developed that at the same time ensures the retention of albumin. Because many middle-sized substances may contribute to micro-inflammation we hypothesized that the use of MCO-Ci influences the inflammatory state in hemodialysis patients.
  
  
  METHODS
  The randomized crossover trial in 48 patients compared MCO-Ci dialysis to High-flux dialysis of 4 weeks duration each plus 8 weeks extension phase. Primary endpoint was the gene expression of TNF-α and IL-6 in peripheral blood mononuclear cells (PBMCs), secondary endpoints were plasma levels of specified inflammatory mediators and cytokines.
  
  
  RESULTS
  After four weeks of MCO-Ci the expression of TNF-α mRNA (Relative quantification (RQ) from 0.92 ± 0.34 to 0.75 ± 0.31, -18.5%, p<0.001)-α and IL-6 mRNA (RQ from 0.78 ± 0.80 to 0.60 ± 0.43, -23.1%, p<0.01) was reduced to a significantly greater extent than with High-flux dialyzers (TNF mRNA-RQ: -14.3%; IL-6 mRNA-RQ: -3.5%). After retransformation of logarithmically transformed data, measurements after MCO were reduced to 82% of those after HF (95% CI 74%-91%). 4 weeks use of MCO-Ci resulted in long-lasting change in plasma levels of several cytokines and other substances with a significant decrease for sTNFR1, kappa and lambda free light chains, urea and an increase for Lp-PLA2 (PLA2G7) compared to High-flux. Albumin levels dropped significantly after 4 weeks of MCO dialysis but increased after additional 8 weeks of MCO dialysis. Twelve weeks treatment with MCO-Ci was well tolerated regarding the number of (S)AEs. In the extension period levels of CRP, TNF-α-mRNA and IL-6 mRNA remained stable in High-flux as well as in MCO-Ci.
  
  
  CONCLUSIONS
  MCO-Ci dialyzers modulate inflammation in chronic HD patients to a greater extent compared to High-flux dialyzers. Transcription of pro-inflammatory cytokines in peripheral leukocytes is markedly reduced and removal of soluble mediators is enhanced with MCO dialysis. Serum albumin concentrations stabilize after an initial drop. These results encourage further trials with longer treatment periods and clinical endpoints.
authors.affiliation: Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Department of Nephrology and Intensive Care Medicine, Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zickler
authors.affiliation: Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Department of Nephrology and Intensive Care Medicine, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schindler
authors.affiliation: Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Department of Nephrology and Intensive Care Medicine, Berlin, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Willy
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: Michael
authors.initials: M
authors.lastname: Hulko
authors.affiliation: Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Boehler
authors.affiliation: Institute for Chemistry, Food Chemistry, Martin-Luther-University Halle, Halle an der Saale, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Glomb
authors.affiliation: Institute for Chemistry, Food Chemistry, Martin-Luther-University Halle, Halle an der Saale, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Liehr
authors.affiliation: Institute for Chemistry, Food Chemistry, Martin-Luther-University Halle, Halle an der Saale, 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 an der Saale, Germany.
authors.forename: Bogusz
authors.initials: B
authors.lastname: Trojanowicz
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle, Halle an der Saale, 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 Internal Medicine II, Martin-Luther-University Halle, Halle an der Saale, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Fiedler
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle, Halle an der Saale, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Girndt
mesh_terms: D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D016207:Cytokines; D008567:Membranes, Artificial; D001613:beta 2-Microglobulin