An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate.
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.
Yang
Wu-Chang
WC
Division of Nephrology, Department of Medicine, Veteran's General Hospital-Taipei, Taiwan, Republic of China.
Yang
Chwei-Shiun
CS
Hou
Chun-Chen
CC
Wu
Tsai-Hung
TH
Young
Eric W
EW
Hsu
Chen H
CH
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
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