Department of Internal Medicine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
J Pharmacol Exp Ther. 2013 Aug;346(2):281-9. doi: 10.1124/jpet.113.204792. Epub 2013 May 22.
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.
慢性肾衰竭（CRF）与继发性甲状旁腺功能亢进和血管钙化的发展有关。我们评估了新型铁基非钙磷酸盐结合剂 PA21 在控制磷钙紊乱和预防尿毒症大鼠血管钙化方面的疗效。用腺嘌呤饮食诱导 CRF 的大鼠随机分为接受 PA210.5%、1.5%或 5%或碳酸钙 3%饮食 4 周的组，并与尿毒症和非尿毒症对照组进行比较。在磷酸盐结合剂治疗 4 周后，所有 CRF 组的血清钙、肌酐和体重均相似。与 CRF 对照组相比，碳酸钙 3%（2.06 mM；P≤0.001）、PA211.5%（2.29 mM；P<0.05）和 PA215%（2.21 mM；P≤0.001）降低了血清磷。PA215%和碳酸钙 3%CRF 组的完整甲状旁腺激素均强烈降低，与 CRF 对照组（3261 pg/ml）相比，分别降低至相似程度（1138 和 1299 pg/ml；均 P≤0.001）。与碳酸钙 3%和 CRF 对照组相比，PA215%CRF 大鼠的血清成纤维细胞生长因子 23 浓度较低。PA215%CRF 大鼠的血管钙化评分低于碳酸钙 3%CRF 大鼠和 CRF 对照组。总之，PA21 在控制磷钙紊乱方面与碳酸钙一样有效，但在预防尿毒症大鼠血管钙化的发展方面更优。因此，PA21 可能是 CRF 患者钙基磷酸盐结合剂的替代物。
