title: Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure.
abstract: Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.
authors.affiliation: Department of Internal Medicine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Phan
authors.affiliation: Department of Internal Medicine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Maillard
authors.affiliation: Division of Nephrology, Bone & Mineral Metabolism, University of Kentucky, Lexington, KY, USA.
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Malluche
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Stehle
authors.affiliation: Vifor (International) Ltd., St. Gallen, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Funk
authors.affiliation: Department of Internal Medicine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004338:Drug Combinations; D005290:Ferric Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006706:Homeostasis / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000652:urine; D007811:Lanthanum / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009026:Mortality; D010710:Phosphates / Q000378:metabolism*; D017208:Rats, Wistar; D000069603:Sevelamer / Q000494:pharmacology / Q000627:therapeutic use*; D013395:Sucrose / Q000494:pharmacology / Q000627:therapeutic use*; D061205:Vascular Calcification / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000652:urine
chemical_list: D004338:Drug Combinations; D005290:Ferric Compounds; D010710:Phosphates; C000599459:sucroferric oxyhydroxide; C119467:lanthanum carbonate; D013395:Sucrose; D005346:Fibroblast Growth Factors; D007811:Lanthanum; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer