PA21, a New Iron-Based Noncalcium Phosphate Binder, Prevents Vascular Calcification in Chronic Renal Failure Rats

• Published in: The Journal of pharmacology and experimental therapeutics 2013-08, Vol.346 (2), p.281-289
• Main Authors: Phan, Olivier, Maillard, Marc, Peregaux, Christine, Mordasini, David, Stehle, Jean-Christophe, Funk, Felix, Burnier, Michel
• Format: Article
• Language: English
• Subjects: Adenine; Animals; Aorta - drug effects; Aorta - pathology; Blood Pressure - drug effects; Calcium - blood; Calcium Carbonate - therapeutic use; Ferric Compounds - therapeutic use; Fibroblast Growth Factors - blood; Heart Rate - drug effects; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - pathology; Male; Parathyroid Hormone - blood; Phosphorus - blood; Rats; Rats, Wistar; Vascular Calcification - pathology; Vascular Calcification - prevention & control
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.113.204792

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.