title: Sevelamer carbonate lowers serum phosphorus effectively in haemodialysis patients: a randomized, double-blind, placebo-controlled, dose-titration study.
abstract: BACKGROUND
  Hyperphosphataemia in patients with advanced chronic kidney disease (CKD) is associated with adverse outcomes, including vascular calcification and higher mortality rates. While phosphate lowering is an integral aspect of CKD management, the efficacy and safety of phosphate binders in a contemporary cohort of Chinese haemodialysis patients (who have different genetics and dietary patterns than other populations) has not been previously described. Moreover, sparse data are available on strategies for optimal dose titration when transitioning from a calcium-based to a polymer-based phosphate binder.
  
  
  METHODS
  This randomized, double-blind, dose-titration study compared sevelamer carbonate (starting dose 800 mg three times daily) with placebo over 8 weeks' duration in Chinese CKD patients on haemodialysis. Patients were required to be using calcium-based binders prior to study start.
  
  
  RESULTS
  In all, 205 patients were randomized (sevelamer, n = 135; placebo, n = 70); mean age was 48.6 years, 61% were male and the mean time on dialysis was 4.4 years. The mean serum phosphorus decreased significantly in patients treated with sevelamer carbonate [change -0.69 ± 0.64 mmol/L (-2.14 ± 1.98 mg/dL)] but remained persistently elevated with placebo [change -0.06 ± 0.57 mmol/L (-0.19 ± 1.76 mg/dL)] (P < 0.0001). When compared with placebo, sevelamer carbonate treatment resulted in statistically significant greater mean reductions from baseline in serum total (-17.1 versus -3.3%) and low-density lipoprotein cholesterol (-33.5 versus-7.6%) (P < 0.0001 for both). Sevelamer carbonate was well tolerated with 96% adherence compared with 97% adherence in the placebo arm. Overall, adverse events experienced by patients in the sevelamer carbonate and placebo treatment groups were similar and consistent with their underlying renal disease.
  
  
  CONCLUSIONS
  This study demonstrated that hyperphosphataemia developed quickly following the cessation of phosphate binders and remained persistently elevated in end-stage CKD in the placebo-treated group. Gradually titrating up sevelamer carbonate from an initial dose of 2.4 g/day to an average daily dose of 7.1 ± 2.5 g/day was well tolerated, safe and efficacious in contemporary Chinese haemodialysis patients.
authors.affiliation: Shanghai Ruijin Hospital, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.forename: Xiongfei
authors.initials: X
authors.lastname: Wu
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Ding
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
authors.forename: Ping
authors.initials: P
authors.lastname: Fu
authors.forename: Gengru
authors.initials: G
authors.lastname: Jiang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.forename: Jianghua
authors.initials: J
authors.lastname: Chen
authors.forename: Bicheng
authors.initials: B
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: La
authors.forename: Fanfan
authors.initials: F
authors.lastname: Hou
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Ni
authors.forename: Junzhou
authors.initials: J
authors.lastname: Fu
authors.forename: Changying
authors.initials: C
authors.lastname: Xing
authors.forename: Xuequing
authors.initials: X
authors.lastname: Yu
authors.forename: Chaoxing
authors.initials: C
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Hunter
authors.forename: Maureen
authors.initials: M
authors.lastname: Dillon
authors.forename: Melissa
authors.initials: M
authors.lastname: Plone
authors.forename: John
authors.initials: J
authors.lastname: Neylan
mesh_terms: D000328:Adult; D000368:Aged; D002614:Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054559:Hyperphosphatemia / Q000150:complications / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011073:Polyamines / Q000008:administration & dosage / Q000627:therapeutic use*; D006435:Renal Dialysis; D000069603:Sevelamer; D055815:Young Adult
chemical_list: D002614:Chelating Agents; D008078:Cholesterol, LDL; D010710:Phosphates; D011073:Polyamines; D010758:Phosphorus; D000069603:Sevelamer
keywords: clinical study; haemodialysis; hyperphosphataemia; placebo; sevelamer carbonate