title: High cut-off dialysis in chronic haemodialysis patients reduces serum procalcific activity.
abstract: Vascular calcification is enhanced in chronic dialysis patients, possibly due to the insufficient removal of various intermediate molecular weight uraemic toxins such as interleukins with conventional membranes. In this study, we assessed the modulation of in vitro vascular calcification with the use of high cut-off (HCO) membranes in chronic dialysis patients.
  
  
  
  In a PERCI trial, 43 chronic dialysis patients were treated with conventional high-flux and HCO filters for 3 weeks in a randomized order following a 2-period crossover design. After each phase, serum predialysis samples were drawn. Calcifying human coronary vascular smooth muscle cells (VSMCs) were incubated with the patient's serum samples. Calcification was assessed with alkaline phosphatase (ALP) and alizarin red staining. In the clinical trial, HCO dialysis reduced the serum levels of the soluble tumour necrosis factor receptor (sTNFR) 1 and 2, vascular cell adhesion molecule 1 (VCAM-1) and soluble interleukin-2 receptor (sIL2R). We therefore investigated the in vitro effects of these mediators on vascular calcification.
  
  
  
  VSMCs incubated with HCO dialysis serum showed a 26% reduction of ALP with HCO serum compared with high-flux serum. Alizarin was 43% lower after incubation with the HCO serum compared with the high-flux serum. While sIL2R and sTNFR 1 and 2 showed no effects on VSMC calcification, VCAM-1 caused a dose-dependent enhancement of calcification.
  
  
  
  The use of HCO dialysis membranes in chronic dialysis patients reduces the procalcific effects of serum on VSMC in vitro. The mechanisms of the strong effect of HCO on in vitro calcification are not completely understood. One factor may be lower levels of VCAM-1 in HCO serum samples, since VCAM-1 was able to induce vascular calcification in our experiments. Neither sTNFR 1, sTNFR 2 nor sIL2R enhance vascular calcification in vitro. Regardless of the mechanisms, our results encourage further studies of highly permeable filters in chronic dialysis patients.
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: Kevin
authors.initials: K
authors.lastname: Willy
authors.affiliation: Department of Internal Medicine II, Martin-Luther-University Halle, Halle, Germany.
authors.forename: Matthias
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: Department of Research and Development, Gambro Dialysatoren GmbH, Hechingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Storr
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; D015415:Biomarkers / Q000378:metabolism; D018592:Cross-Over Studies; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D006435:Renal Dialysis / Q000009:adverse effects*; D061205:Vascular Calcification / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D007378:Interleukins
keywords: atherosclerosis; chronic haemodialysis; coronary artery disease; inflammation; vascular calcification