New phosphate binding agents: ferric compounds.
Several prior studies suggest that ferric compounds bind dietary phosphate and possess clinical potential as phosphate binding agents. Therefore, this study was conducted to measure the effect of several ferric compounds on intestinal phosphate binding and absorption. Balance studies lasting 2 to 4 wk were performed in normal and azotemic (achieved by subtotal nephrectomy) rats maintained on a 1.02% phosphorus diet supplemented with ferric salts (formulated to 0.95% Fe) or no ferric salt (control). In rats with normal renal function (average creatinine clearance, 4.0 ml/min per kg), the average net intestinal absorption of phosphate over all balance periods was 103.3 mg/d for the control group versus 84.7 mg/d for the ferric citrate group (P < 0.005). In the azotemic rats (average creatinine clearance, 3.3 ml/min per kg), the average net intestinal absorption of phosphate over all balance periods was significantly lower for the three ferric groups than the control groups (P < or = 0.02): 95.3 mg/d for the control group versus 75.6 mg/d for the ferric ammonium citrate-treated group (P = 0.058), 77.0 mg/d for the ferric citrate-treated group (P = 0.057), and 62.5 mg/d for the ferric chloride-treated group (P < 0.002). Urinary phosphate excretion fell, sometimes to an even greater extent than did intestinal absorption, yielding no net reduction in phosphate balance in these growing, young animals with relatively preserved renal function. Calcium balance was largely unaffected by the ferric compounds. There were trends toward decreased serum phosphorus and parathyroid hormone concentrations and increased iron and hematocrit in the ferric-treated azotemic groups. All tested ferric compounds were well tolerated, but animal growth was stunted in the ferric chloride animals compared with the control group. Phosphate binding was estimated at 85 to 180 mg per gram of elemental iron, which is comparable to other phosphate binding agents. Ferric salts decrease net intestinal phosphate absorption and hold promise for the treatment of phosphate retention in patients with renal failure.
Hsu
C H
CH
Department of Internal Medicine, University of Michigan Medical School, VA Medical Center, Ann Arbor, USA. hsuc@umich.edu
Patel
S R
SR
Young
E W
EW
D000704:Analysis of Variance; D000818:Animals; D001665:Binding Sites; D004032:Diet; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000378:metabolism* / Q000494:pharmacology*; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014511:Uremia / Q000188:drug therapy*
D005290:Ferric Compounds; D010710:Phosphates