title: PA21, a new iron-based noncalcium phosphate binder, prevents vascular calcification in chronic renal failure rats.
abstract: Chronic renal failure (CRF) is associated with the development of secondary hyperparathyroidism and vascular calcifications. We evaluated the efficacy of PA21, a new iron-based noncalcium phosphate binder, in controlling phosphocalcic disorders and preventing vascular calcifications in uremic rats. Rats with adenine-diet-induced CRF were randomized to receive either PA21 0.5, 1.5, or 5% or CaCO3 3% in the diet for 4 weeks, and were compared with uremic and nonuremic control groups. After 4 weeks of phosphate binder treatment, serum calcium, creatinine, and body weight were similar between all CRF groups. Serum phosphorus was reduced with CaCO3 3% (2.06 mM; P ≤ 0.001), PA21 1.5% (2.29 mM; P < 0.05), and PA21 5% (2.21 mM; P ≤ 0.001) versus CRF controls (2.91 mM). Intact parathyroid hormone was strongly reduced in the PA21 5% and CaCO3 3% CRF groups to a similar extent (1138 and 1299 pg/ml, respectively) versus CRF controls (3261 pg/ml; both P ≤ 0.001). A lower serum fibroblast growth factor 23 concentration was observed in the PA21 5%, compared with CaCO3 3% and CRF, control groups. PA21 5% CRF rats had a lower vascular calcification score compared with CaCO3 3% CRF rats and CRF controls. In conclusion, PA21 was as effective as CaCO3 at controlling phosphocalcic disorders but superior in preventing the development of vascular calcifications in uremic rats. Thus, PA21 represents a possible alternative to calcium-based phosphate binders in CRF patients.
authors.affiliation: Department of Internal Medicine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. olivier.phan@chuv.ch
authors.forename: Olivier
authors.initials: O
authors.lastname: Phan
authors.forename: Marc
authors.initials: M
authors.lastname: Maillard
authors.forename: Christine
authors.initials: C
authors.lastname: Peregaux
authors.forename: David
authors.initials: D
authors.lastname: Mordasini
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Stehle
authors.forename: Felix
authors.initials: F
authors.lastname: Funk
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
mesh_terms: D000225:Adenine; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002119:Calcium Carbonate / Q000627:therapeutic use; D005290:Ferric Compounds / Q000627:therapeutic use*; D005346:Fibroblast Growth Factors / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D061205:Vascular Calcification / Q000473:pathology / Q000517:prevention & control*
chemical_list: D005290:Ferric Compounds; C505605:Fgf23 protein, rat; C552479:PA21 compound; D010281:Parathyroid Hormone; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D002119:Calcium Carbonate; D000225:Adenine; D002118:Calcium