长疗程西那卡塞治疗维持性血液透析患者难治性继发性甲状旁腺功能亢进症的临床观察

Clinical Efficacy of Long-term Cinacalcet Treatment for Refractory Secondary Hyperparathyroidism in Maintenance Hemodialysis Patients

目的观察西那卡塞对维持性血液透析患者难治性继发性甲状旁腺功能亢进症(SHPT)的长期疗效。方法选取2015年4月—2017年3月在厦门大学附属第一医院治疗的合并难治性SHPT的维持性血液透析患者11例为研究对象。西那卡塞初始剂量为25.0 mg/d,每4周根据全段甲状旁腺激素(i PTH)、血钙、血磷调整剂量,调整范围为加减12.5~25.0 mg/d,最大用药量不超过100.0 mg/d,治疗目标为i PTH在150~300 pg/ml;血钙、血磷降至参考范围后决定是否联用骨化三醇。监测治疗期间i PTH、血钙、血磷、碱性磷酸酶(ALP)、血清清蛋白(ALB)、血红蛋白(Hb)、尿素、血肌酐水平变化,共随访84周。结果 11例患者初始i PTH水平为(1 375±352)pg/ml,末期为(245±82)pg/ml,达标均值为(243±47)pg/ml,首次达标时间为12~84周;西那卡塞最大剂量(46.3±20.4)mg/d,末期剂量(20.0±13.4)mg/d,最大剂量治疗时间4~36周;10例患者联用骨化三醇。西那卡塞剂量在第8周达到最大,较初始剂量明显增加,在第60~84周时下降至初始剂量。骨化三醇剂量在第36~84周较初始剂量明显增加。患者治疗后各周i PTH、血钙、血磷水平均低于初始水平,治疗后第60~84周,ALP水平低于初始水平(P<0.05)。治疗前后ALB、Hb、尿素、血肌酐水平比较,差异无统计学意义(P>0.05)。结论长疗程的西那卡塞能有效治疗维持性血液透析患者难治性SHPT,联用骨化三醇效果更佳;随着治疗期间i PTH的下降,维持期西那卡塞剂量减少。

Objective To investigate the efficacy of long-term cinacalcet treatment for refractory secondary hyperparathyroidism(SHPT)patients with maintenance hemodialysis.Methods We selected 11 maintenance hemodialysis patients with refractory SHPT from the First Affiliated Hospital of Xiamen University between April 2015 and March 2017.All of them received cinacalcet treatment.The initial dose of cinacalcet was 25.0 mg/d,which was adjusted according to intact parathyroid hormone(iPTH),serum calcium and phosphorus levels every 4 weeks.The dose adjustment(increased or reduced)ranged from 12.5 to 25.0 mg/d,and the maximum dose did not exceed 100.0 mg/d.The treatment goal was to control iPTH within a range of 150-300 pg/ml.After serum calcium and phosphorus decreased to the reference range,calcitriol was initiated in some patients.The following laboratory indices were monitored during treatment:iPTH,serum calcium,serum phosphorus,alkaline phosphatase(ALP),albumin(ALB),hemoglobin(Hb),pre-dialysis urea nitrogen and pre-dialysis creatinine.Follow-up lasted for 84 weeks.Results Among the participants,the baseline,final,and average standardized iPTH levels were(1 375±352)pg/ml,(245±82)pg/ml and(243±47)pg/ml,respectively;the time for first achieving iPTH level within the standardized range were at 12-84 weeks after treatment;the mean maximum dose and final dose of cinacalcet was(46.3±20.4)mg/d,(20.0±13.4)mg/d,respectively;treatment duration with the maximum dose was 4-36 weeks.Ten patients received combination therapy with cinacalcet and calcitriol.The dose of cinacalcet reached a maximum at the 8th week,which increased a lot compared with the initial dose,but it decreased to the initial level at 60-84 weeks.The dose of calcitriol at 36-84 weeks also increased compared with the initial dose.iPTH,serum calcium and phosphorus levels at various times after treatment were all lower than baseline(P<0.05).At 60-84 weeks,ALP level was lower than baseline(P<0.05).The levels of ALB,Hb,pre-dialysis urea nitrogen and pre-dialysis creatinine before and after treatment did not differ significantly(P>0.05).Conclusion Long-term cinacalcet treatment was effective for refractory SHPT in maintenance hemodialysis patients.Combination of cinacalcet and calcitriol achieved better efficacy.With the decrease of iPTH,the maintenance dose of cinacalcet could be reduced.