title: Serum sclerostin: relation with mortality and impact of hemodiafiltration.
abstract: BACKGROUND
  The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated.
  
  
  METHODS
  In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl.
  
  
  RESULTS
  The mean (±standard deviation) age of 396 test subjects was 63.6 (±13.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31-0.86, P = 0.01)]. Stratified models showed a stable sScl in patients treated with HD (Δ +2.9 pmol/L/year, 95% CI -0.5 to +6.3, P = 0.09) and a decreasing concentration in those treated with HDF (Δ -4.5 pmol/L/year, 95% CI -8.0 to -0.9, P = 0.02). The relative change in the latter group was related to the magnitude of the convection volume.
  
  
  CONCLUSIONS
  (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume.
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lotte
authors.initials: L
authors.lastname: Lips
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research VU University Medical Center (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Camiel L M
authors.initials: CLM
authors.lastname: de Roij van Zuijdewijn
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research VU University Medical Center (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Piet M
authors.initials: PM
authors.lastname: Ter Wee
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.affiliation: Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Blankestijn
authors.affiliation: Department of Internal Medicine, Maasstad Hospital, Rotterdam, The Netherlands.
authors.forename: Marinus A
authors.initials: MA
authors.lastname: van den Dorpel
authors.affiliation: Centre Hospitalier Universitaire de Lyon, Pierre Benite, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Fouque
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Renate
authors.initials: R
authors.lastname: de Jongh
authors.affiliation: Centre Hospitalier Universitaire de Lyon, Pierre Benite, France.
authors.forename: Solenne
authors.initials: S
authors.lastname: Pelletier
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research VU University Medical Center (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research VU University Medical Center (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Menso J
authors.initials: MJ
authors.lastname: Nubé
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research VU University Medical Center (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Muriel P C
authors.initials: MPC
authors.lastname: Grooteman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D018481:Convection; D005260:Female; D005819:Genetic Markers; D017583:Hemodiafiltration / Q000009:adverse effects* / Q000401:mortality*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human
keywords: convection volume; haemodiafiltration; haemodialysis; mortality; sclerostin