碳酸镧应用于高磷血症维持性血液透析患者的长期临床疗效和安全性

Long-term clinical efficacy and security of lanthanum carbonate in treatment of hyperphosphatemia patients undergoing maintenance hemodialysis

目的评估碳酸镧长期应用于高磷血症维持性血液透析(MHD)患者的临床疗效和安全性。方法 MHD患者56例,血清磷>1.78 mmol·L-1,随机分为两组。碳酸镧组35例,予碳酸镧咀嚼片,起始剂量750 mg,bid,总剂量<3 000 mg·d-1。碳酸钙组21例,予碳酸钙D3片,起始剂量600 mg,bid,总剂量<3 000 mg·d-1。根据血磷和血钙检测结果调整药物剂量,疗程均为36个月。观察两组治疗前和治疗1、3、6、12、24、36个月患者血清钙、磷、全段甲状旁腺激素(i PTH)、成纤维细胞生长因子23(FGF-23)水平变化情况和不良反应,并在治疗前和治疗36个月行心脏彩超和螺旋CT,评估左心室肥厚和冠状动脉钙化状况。结果共39例患者完成本次研究,碳酸镧组25例,碳酸钙组14例。与治疗前比较,两组血磷水平治疗1个月起即下降(P<0.05)。碳酸镧组治疗期间血钙水平无明显变化,而碳酸钙组于治疗6个月血钙开始增高(P<0.05)。碳酸镧组i PTH水平治疗6个月起下降(P<0.05),碳酸钙组治疗期间i PTH水平无明显变化。碳酸镧组FGF-23水平治疗1个月起即下降(P<0.05),碳酸钙组于治疗12个月起下降(P<0.05)。治疗36个月,碳酸镧组血磷、钙、i PTH、FGF-23水平均低于碳酸钙组(P<0.05)。治疗前后血磷水平变化值和血FGF-23水平变化值进行相关分析,两者呈正相关(r=0.605,P<0.01)。治疗36个月,两组左心室质量指数和冠状动脉钙化评分均较治疗前上升(P<0.05),但碳酸镧组两项指标的进展幅度均小于碳酸钙组(P<0.05)。两组均无严重不良反应发生。结论对于高磷血症MHD患者,碳酸镧降血磷效果优于碳酸钙,且能同时降低血FGF-23和i PTH水平,而不引起血钙蓄积,还能够延缓MHD患者左心室肥厚和冠状动脉硬化的进展。

AIM To evaluate the long-term clinical efficacy and safety of lanthanum carbonate （LC） in maintenance hemodialysis （MHD） patients with hyperphosphatemia. METHODS A total of 56 MHD patients with hyperphosphatemia （serum phosphorus 〉 1.78 mmol. L-1） were randomly divided into two groups. LC group （n = 35） were given LC chewable tablets （starting dose 750 mg, po, bid, total dose 〈 3 000 mg.d-1） for 36 months. The calcium carbonate （CC） group （n = 21） were given CC and vitamin D3 tablets （starting dose 600 rag, po, bid, total dose 〈 3 000 mg .d-1） for 36 months. The dosage adjustment was according to the levels of phosphorus and calcium. Serum levels of calcium, phosphorus, intact parathyroid hormone （iPTH） and fibroblast growth factor 23 （FGF-23）were measured before and 1, 3, 6, 12, 24, 36 month after the treatment. Echocardiography and CT scan were used to assess the status of left ventricular hypertrophy and calcification of coronary artery before and 36 month after the treatment. RESULTS A total of 39 MIlD patients were analyzed, 25 patients in the LC group and 14 patients in the CC group. Compared with those before the treatment, the levels of serum phosphorus were significantly decreased in both group after the first month treatment （P 〈 0.05）. During the 36 months treatment period, the levels of serum calcium were no significantly change in the LC group, but the levels of serum calcium were significantly increased in the CC group after 6 months treatment. The levels of iPTH were significantly decreased in the LC group after 6 months treatment （P 〈 0.05）, and the levels of iPTH were no significantly change in the CC group during 36 months treatment. The levels of FGF-23 were significantly decreased in the LC group after 1 month treatment （P 〈 0.05）, and were also significantly decreased in the CC group after 12 months treatment （P 〈 0.05）. After 36 months treatment, the levels of serum phosphorus, calcium, iPTI-I and FGF- 23 in the LC group were significantly lower than those in the CC group （P 〈 0.05）. There was a positive correlation between the changes in FGF-23 and phosphorus concentrations before and after the treatment （r = 0.605, P 〈 0.01 ）. After 36 months treatment, the left ventricular mass index （LVMI） and coronary artery calcification score （CACS） were significantly increased in all patients （P 〈 0.05）, while the LVMI and CACS in the LC group were lower than those in the CC group （P 〈 0.05）. No serious adverse reactions occurred in both groups. CONCLUSION The effect of LC decreasing the serum phosphorus is better than CC for MHD patients with hyperphosphatemia. And LC can decrease the serum FGF- 23 and iPTH levels without causing hypercalcemia, simultaneously can reduce the progress of left ventricular hypertrophy and coronary artery calcification in MHD patients.