title: An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate.
abstract: BACKGROUND
  Hyperphosphataemia contributes to secondary hyperparathyroidism and renal osteodystrophy in patients with end-stage renal disease (ESRD). Calcium salts are widely employed to bind dietary phosphate (P) but they may promote positive net calcium balance and metastatic calcification. We recently reported that ferric compounds bind intestinal phosphate in studies of normal and azotemic rats.
  
  
  METHODS
  To extend this observation, we performed an open-label, random order, crossover comparison study of ferric citrate and calcium carbonate in haemodialysis patients from two teaching hospitals. The study sample consisted of 23 women and 22 men with an average age of 52.5 +/- 11.8 (SD) years and an average weight of 54.5 +/- 10.7 kg. All forms of iron therapy were discontinued. Two weeks before the study, patients were instructed to discontinue all P-binding agents. The patients were randomly assigned to receive either calcium carbonate (3 g/day) or ferric citrate (3 g/day) for 4 weeks followed by a 2 week washout period, and then crossed over to the other P-binding agent for 4 weeks.
  
  
  RESULTS
  From a baseline concentration of 5.6 +/- 1.5 mg/dl, the serum P increased during the washout period to 7.2 +/- 1.9 mg/dl prior to calcium carbonate treatment, and to 6.7 +/- 1.9 mg/dl prior to ferric citrate treatment. The serum P concentration fell significantly during treatment with both calcium carbonate (7.2 +/- 1.9 to 5.2 +/- 1.5 mg/dl, P<0.0001) and ferric citrate (6.7 +/- 1.9 to 5.7 +/- 1.6 mg/dl, P<0.0001). The results were not influenced by order of treatment. Under the conditions of the study protocol, ferric citrate was less effective than calcium carbonate at lowering the serum phosphate concentration. The serum Ca concentration increased during treatment with calcium carbonate but not ferric citrate. Ferric citrate treatment did not affect the serum concentration of aluminium. Ferric citrate treatment was associated with mild and generally tolerable gastrointestinal symptoms.
  
  
  CONCLUSIONS
  Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients. Further studies are needed to find the optimal dose.
authors.affiliation: Division of Nephrology, Department of Medicine, Veteran's General Hospital-Taipei, Taiwan, Republic of China.
authors.forename: Wu-Chang
authors.initials: WC
authors.lastname: Yang
authors.forename: Chwei-Shiun
authors.initials: CS
authors.lastname: Yang
authors.forename: Chun-Chen
authors.initials: CC
authors.lastname: Hou
authors.forename: Tsai-Hung
authors.initials: TH
authors.lastname: Wu
authors.forename: Eric W
authors.initials: EW
authors.lastname: Young
authors.forename: Chen H
authors.initials: CH
authors.lastname: Hsu
mesh_terms: D000328:Adult; D002119:Calcium Carbonate / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D002130:Calcium Phosphates / Q000097:blood; D002136:Calcium, Dietary / Q000008:administration & dosage; D018592:Cross-Over Studies; D005260:Female; D005290:Ferric Compounds / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D016226:Phosphorus, Dietary / Q000008:administration & dosage; D006435:Renal Dialysis
chemical_list: D002130:Calcium Phosphates; D002136:Calcium, Dietary; D005290:Ferric Compounds; D016226:Phosphorus, Dietary; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D010758:Phosphorus; C025314:ferric citrate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D002119:Calcium Carbonate; C485829:calcium phosphate, dibasic, anhydrous