title: Pleiotropic effects of sevelamer beyond phosphate binding in end-stage renal disease patients: a randomized, open-label, parallel-group study.
abstract: OBJECTIVE
  Hyperphosphataemia in end-stage renal disease (ESRD) is a major contributor to the development of cardiovascular disease. It has been proposed that the phosphate binder sevelamer has pleiotropic properties. The aim of this study was to evaluate the effects of sevelamer compared with calcium acetate on serum lipid profiles, uric acid and reactive oxygen species in haemodialysis patients with hyperphosphataemia.
  
  
  METHODS
  An 8-week, randomized, open-label, parallel-group study was conducted after a 2-week washout period. A total of 52 patients with ESRD on maintenance haemodialysis were screened for enrolment; 26 patients were randomized to each of the sevelamer and calcium acetate groups. Reactive oxygen species (ROS) production, i.e. superoxide and hydrogen peroxide (H2O2)-related radicals, were detected by chemiluminescence measurement with lucigenin and luminol, respectively.
  
  
  RESULTS
  There were no significant differences between treatment groups in changes in serum phosphorus (p=0.378) and adjusted serum calcium levels (p=0.980), but there were more hypercalcaemic events in the calcium acetate group (12.0% vs 3.7%) during treatment. Total serum cholesterol (p<0.001) and low-density lipoprotein (LDL) cholesterol (p<0.001) levels decreased significantly compared with baseline in the sevelamer group. The decreases in total serum cholesterol and LDL cholesterol were correlated with the reductions in serum phosphorus levels during sevelamer treatment (correlation coefficient [r]=0.266 and 0.386, respectively). Serum uric acid decreased significantly in the sevelamer group (p=0.020), and this change was correlated with serum phosphorus changes (r=0.458). Decreases in plasma H2O2-related radicals, the major oxidative stressor in ROS (p<0.001), but not superoxide (p=0.593), were observed after sevelamer treatment.
  
  
  CONCLUSIONS
  The improvements in multiple lipid surrogates, uric acid and ROS seen in this study show that sevelamer is a promising therapy for treatment of hyperphosphataemia in maintenance haemodialysis patients with a high risk of cardiovascular disease.
authors.affiliation: Department of Traumatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Lin
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Kan
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Chen
authors.forename: Tzong-Shinn
authors.initials: TS
authors.lastname: Chu
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Hung
authors.forename: Tun-Jun
authors.initials: TJ
authors.lastname: Tsai
authors.forename: Kwan-Dun
authors.initials: KD
authors.lastname: Wu
authors.forename: Ming-Shiou
authors.initials: MS
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood; D002614:Chelating Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood; D011073:Polyamines / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D006435:Renal Dialysis; D000069603:Sevelamer; D014527:Uric Acid / Q000097:blood
chemical_list: D002614:Chelating Agents; D008055:Lipids; D011073:Polyamines; D017382:Reactive Oxygen Species; D014527:Uric Acid; D010758:Phosphorus; D000069603:Sevelamer; D002118:Calcium