JASN：磷结合剂对慢性肾病中期患者的治疗效果

　　临床上给予CKD患者使用磷酸盐结合剂是因为考虑较高水平的磷酸盐可能与CKD患者的死亡率风险相关，但是在CKD人群中使用磷酸盐的具体安全性以及效应却未得到明确的结论。发表在《美国肾脏病学会杂志》（J Am Soc Nephrol. 2012 Aug;23(8):1407-15.）上的一篇研究中，研究者观察了磷酸盐对中度到晚期的CKD患者体内矿物代谢和血管钙化等相关指标的影响。

　　研究将eGFR在20–45 ml/min per 1.73 m2的148名CKD患者随机分为醋酸钙、碳酸镧、醋酸司维拉姆以及安慰剂。主要观察的结果是使用磷酸盐时以及使用后3/6/9个月患者平均血清磷水平，其中治疗组的目标是血清磷从平均基础值4.2 mg/dl降至3.9 mg/dl，安慰剂组从平均基础值4.2 mg/dl降至4.1 mg/dl。

　　磷酸盐结合剂可平均降低患者24小时尿磷20%，而安慰剂无此变化。治疗组的甲状旁腺激素水平在治疗前后一直保持稳定状态，而安慰剂组则增加了(P=0.002)。治疗组对胞浆C端成纤维细胞生长因子23水平无显著影响，但是却显著增加了冠状动脉和腹主动脉的钙化（治疗组和安慰剂冠脉平均钙化分别增加了18.1% 、0.6%，P=0.05；腹主动脉分别增加了15.4% 、3.4%, P=0.03）。

　　由此可见，磷酸盐结合剂可以显著降低正常或正常高限血清磷CKD患者血清和尿中磷的水平、缓解激发性甲旁亢的发生发展，但是却同时促进了血管钙化的进展。看来磷酸盐在CKD患者中治疗的安全性以及疗效还需要进一步的研究来明确。

Effects of Phosphate Binders in Moderate CKD

Abstract

Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20–45 ml/min per 1.73 m2 to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.