不同方式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的对比性研究

Comparative study of different methods in the treatment of refractory secondary hyperparathyroidism in maintenance hemodialysis patients

目的探讨帕立骨化醇联合盐酸西那卡塞治疗难治性继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)的有效性及安全性;同时与甲状旁腺切除术(parathyroidectomy,PTX)进行疗效对比。方法回顾性分析2013年12月至2016年6月在哈尔滨医科大学附属第一医院血液净化中心行维持性血液透析(maintenance hemodialysis,MHD)的难治性SHPT患者,PTX组11例,帕立骨化醇联合西那卡塞(药物)组13例,记录年龄、透析龄、治疗前1周、治疗后1周、1月、3月及6月血清钙(calcium,Ca)、磷(phosphorus P)、钙磷乘积(Ca×P)、全段甲状旁腺素(intact parathyroid hormone,i PTH)水平、碱性磷酸酶(alkaline phosphatase,AKP)及临床症状,根据复查结果调整药量。比较两组相同时间点及不同治疗方式上述指标。结果与治疗前相比,PTX组治疗后1周、1月、3月及6月血清Ca、Ca×P、i PTH及AKP水平降低,差异有统计学意义(血清Ca:F=18.908,P<0.001;Ca×P:F=21.884,P<0.001;血清i PTH:F=24.251,P<0.001;血清AKP:F=95.459,P=0.001);药物组治疗后1月、3月及6月血清Ca及i PTH水平显著降低,差异有统计学意义(血Ca:F=7.671,P<0.001;血清i PTH:F=4.037,P=0.006);血清P及AKP水平整个治疗期间差异不显著(血清P:F=0.378,P=0.824;血清AKP:F=0.718,P=0.583)。治疗6月后两组(PTX组比药物组)血清Ca[(2.40±0.15)mmol/L比(2.44±0.14)mmol/L、t=-0.797,P=0.434]、P[(1.98±0.25)mmol/L比(2.20±0.39)mmol/L,t=-1.616,P=0.120]及Ca×P[(4.74±0.27)mmol^2/L^2比(5.38±1.02)mmol^2/L^2,t=-1.740,P=0.096]及AKP[(85.50±38.43)比(113.33±36.83)U/L,t=-1.815,P=0.083]无差异;血清i PTH差异显著[(525.81±242.12)pg/ml比(809.22±372.87)pg/ml,t=-2.161,P=0.042]。结论帕立骨化醇联合盐酸西那卡塞与PTX均能不同程度治疗难治性SHPT,PTX能够更快的改善高Ca、P及骨代谢,远期疗效需扩大样本量及观察时间进一步评价。

Objective To investigate the efficacy and safety of paricalcitol plus cinacalcet and to compare the curative effect of paricalcitol plus cinacalcet with parathyroidectomy（PTX） for the treatment of refractory secondary hyperparathyroidism（SHPT） in patients on maintenance haemodialysis（MHD）. Methods MHD patients with refractory SHPT treated in the First Affiliated Hospital of Harbin Medical University between Dec. 2013 and Jun. 2016 were enrolled in this retrospective study. Patients were divided into two groups： PTX group（n=11） and medication group（paricalcitol plus cinacalcet, n=13）. Efficacy of the treatment was evaluated by changes of serum calcium（Ca）, phosphorus（P）, calcium-phosphate product, intact parathyroid hormone（i PTH）, alkaline phosphatase（AKP） and clinical symptom before and after paricalcitol plus cinacalcet therapy for one week, 1, 3 and 6 months. Age, duration of dialysis, and plasma albumin were collected. Drug doses were adjusted according to the results of laboratory examinations. We compared the clinical indicators at the same treatment time points between the two groups. Results In PTX group after the surgery for one week,1, 3 and 6 months, serum Ca, Ca×P product, i PTH and AKP decreased significantly（serum Ca： F=18.908, P〈0.001; Ca × P： F=21.884, P〈0.001; serum i PTH： F=24.251, P〈0.001; serum AKP： F=95.459, P=0.001）. In medication group after the treatment for 1, 3 and 6 months, serum Ca and i PTH decreased significantly（serum Ca： F=7.671, P〈0.00; serum i PTH： F=4.037, P=0.006）; serum P and AKP remained stable throughout the treatment period（serum P： F=0.378, P=0.824; serum AKP： F=0.718, P=0.583）. Compared the differences between PTX group and medication group after the treatment for 6 months, serum Ca, serum P, Ca×P product and AKP had no significant differences（serum Ca： 2.40±0.15 mmol/L vs. 2.44±0.14 mmol/L, t=-0.797, P=0.434; serum P： 1.98±0.25 mmol/L vs. 2.20±0.39 mmol/L, t=-1.616, P=0.120; Ca×P： 4.74±0.27 mmol2/L2 vs.5.38±1.02 mmol^2/L^2, t=-1.740, P=0.096; serum AKP： 85.50±38.43 U/L vs. 113.33±36.83 U/L, t=-1.815, p=0.083）, but serum i PTH differed significantly（525.81±242.12 pg/ml vs. 809.22±372.87 pg/ml, t=-2.161, P=0.042）. Conclusions Both paricalcitol plus cinacalcet and PTX were able to treat the refractory SHPT. PTX quickly improved the higher serum Ca and P and bone metabolism. However, the long-term effects should be evaluated further through expanding the sample size and the observation period.