帕立骨化醇治疗血液透析患者伴继发性甲状旁腺功能亢进的疗效观察
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摘要
目的探讨帕立骨化醇治疗血液透析伴继发性甲状旁腺功能亢进(secondary hyperparathyroidism, SHPT)患者的有效性及安全性。方法纳入北京市第六医院维持性血液透析合并SHPT患者11例(帕立骨化醇起始剂量按0.04～0.10μg/kg给药)。治疗起始后,监测血清全段甲状旁腺素(intact parathyroid hormone,iPTH)、钙、磷、碱性磷酸酶(alkaline phosphatase,ALP)水平并评估视觉模拟法(visual analogue scale,VAS)评分。本观察性研究的主要疗效指标为治疗12周后,iPTH水平较基线下降>50%的患者比例。次要疗效指标包括:治疗12周后,iPTH平均水平较基线的下降幅度;iPTH水平降至150～300pg/m1的患者比例;研究结束时不良事件的发生率。结果 11例患者基线平均iPTH水平为(1283.56±443.71)pg/ml,接受12周帕立骨化醇治疗后,平均iPTH水平降至(346.38±223.72)pg/ml,差异有统计学意义(t=6.578,P<0.001),下降73.01%。全部11例患者的终点iPTH水平较基线下降幅度均超过50%,达到主终点的患者比例为100%。研究结束时,共有7例患者的iPTH水平降至150～300pg/ml范围内,达标比例为63.64%。11例患者的终点血清钙、磷及ALP的平均水平较基线无显著变化,均无统计学意义(t值分别是2.952,1.305,1.513;P值分别是0.088,0.206,0.145),VAS评分较基线显著降低(t=15.976,P<0.001)。仅有1例患者发生高钙血症(血钙水平为2.64mmol/L)。结论本研究证实,帕立骨化醇能够有效治疗血液透析患者SHPT,显著降低血清iPTH水平和患者骨痛VAS评分,同时血钙、磷变化相对稳定。
Objectives To investigate the efficacy and safety of paricalcitol in the treatment of hemodialysis patients complicated with secondary hyperparathyroidism(SHPT). Methods Eleven maintenance hemodialysis patients with SHPT treated in Beijing Sixth Hospital were enrolled in this study. Their initial dose of paricalcitol was 0.04-0.10 μg/kg. During the treatment period, serum levels of intact parathyroid hormone(iPTH), calcium, phosphorus, alkaline phosphatase(ALP) were monitored, and the score of visual analogue scale(VAS) was used to assess patient's condition. The major efficacy parameter was the decrease of iPTH more than 50% of baseline value after 12 weeks of the treatment. The secondary efficacy parameters included the average range of iPTH below baseline value, the proportion of the patients with the i PTH level within150～300 pg/ml after 12 weeks of the treatment, as well as the incidence of adverse events at the end of the study. Results The average baseline iPTH level of the 11 patients was 1283.56 ± 443.71 pg/ml. After 12 weeks of paricalcitol treatment, the average i PTH level decreased by 73.01% of the baseline value to 346.38±223.72 pg/ml(t=6.578, P<0.001). In all of the 11 patients, the endpoint iPTH level decreased by more than50% of the baseline value. At the endpoint of the study, iPTH levels reduced to 150-300 pg/ml in 7 of the 11 patients and reached the compliance rate in 63.64% patients; serum calcium(t=2.952, P=0.088), phosphorus(t=1.305, P=0.206) and ALP(t=1.513, P=0.145) had no significant differences compared to the baseline values in the 11 patients; VAS score was significantly lower than baseline value(t=15.976, P<0.001). One patient developed hypercalcemia(serum calcium 2.64 mmol/L). Conclusions This study confirmed that paricalcitol can effectively treat SHPT in hemodialysis patients. It can reduce serum iPTH level and the bone pain VAS score, without changes of serum calcium and phosphorus.
Objectives To investigate the efficacy and safety of paricalcitol in the treatment of hemodialysis patients complicated with secondary hyperparathyroidism(SHPT). Methods Eleven maintenance hemodialysis patients with SHPT treated in Beijing Sixth Hospital were enrolled in this study. Their initial dose of paricalcitol was 0.04-0.10 μg/kg. During the treatment period, serum levels of intact parathyroid hormone(iPTH), calcium, phosphorus, alkaline phosphatase(ALP) were monitored, and the score of visual analogue scale(VAS) was used to assess patient's condition. The major efficacy parameter was the decrease of iPTH more than 50% of baseline value after 12 weeks of the treatment. The secondary efficacy parameters included the average range of iPTH below baseline value, the proportion of the patients with the i PTH level within150～300 pg/ml after 12 weeks of the treatment, as well as the incidence of adverse events at the end of the study. Results The average baseline iPTH level of the 11 patients was 1283.56 ± 443.71 pg/ml. After 12 weeks of paricalcitol treatment, the average i PTH level decreased by 73.01% of the baseline value to 346.38±223.72 pg/ml(t=6.578, P<0.001). In all of the 11 patients, the endpoint iPTH level decreased by more than50% of the baseline value. At the endpoint of the study, iPTH levels reduced to 150-300 pg/ml in 7 of the 11 patients and reached the compliance rate in 63.64% patients; serum calcium(t=2.952, P=0.088), phosphorus(t=1.305, P=0.206) and ALP(t=1.513, P=0.145) had no significant differences compared to the baseline values in the 11 patients; VAS score was significantly lower than baseline value(t=15.976, P<0.001). One patient developed hypercalcemia(serum calcium 2.64 mmol/L). Conclusions This study confirmed that paricalcitol can effectively treat SHPT in hemodialysis patients. It can reduce serum iPTH level and the bone pain VAS score, without changes of serum calcium and phosphorus.
引文
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[7]云扬,张晨,李德天,等.帕立骨化醇对维持性血液透析患者炎症状态及氧化应激的影响[J].中国血液净化,2018,17(10):677-681.
[8]Ketteler M,Martin KJ,Wolf M,et al.Paricalcitol vs.cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis:result of the IMPACT SHPTstudy[J].Nephrol Dial Transplant,2012,27:3270-3278.
[9]Yucheng Yan,Jiaqi Qian,Nan Chen,et al.Efficacy and initial dose determination of paricalcitol for treatment of secondary hyperparathyroidism in Chinese subjects[J].Clin Nephrol,2014,81(1):20-29.
[10]张玉梅,宋鲁平.康复评定常用量表[M].北京.科学技术文献出版社,2018:464-465.
[11]Biggar P,Kovarik J,Klauser-Braun R,et al.Paricalcitol Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients:A German-Austrian,Single-Arm,OpenLabel,Prospective,Noninterventional,Observational Study[J].Nephron Clin Pract,2014,126:39-50.
[12]Ketteler M,Martin KJ,Cozzolino M,et al.Paricalcitol versus cinacalcet plus low-dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis:study design and baseline characteristics of the IMPACT SHPT study[J].Nephrol Dial Transplant,2012,27(5):1942-1949.
[13]王泰娜,徐斌,刘志红,等.帕立骨化醇治疗血液透析患者伴继发性甲状旁腺功能亢进[J].肾脏病与透析肾移植杂志,2015,24(1):1-5.
[14]郝娟,程叙扬,左力,等.帕立骨化醇不同给药方式治疗继发性甲状旁腺功能亢进症的对照研究[J].中国血液净化,2015,14(9):540-544.
[2]Bertram L.Kasiske,Blanche Chavers,Robert Foley,et al.K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease[J].Am J Kidney Dis,2003,42(4 Suppl 3):S92-93.
[3]周加军,张凌.活性维生素D及其类似物在CKD-MBD中的应用[J].中国血液净化,2018,17(6):370-373.
[4]王莉,李贵森,刘志红.中华医学会肾脏病学分会慢性肾脏病矿物质与骨异常诊治指导[J].肾脏病与透析肾移植杂志,2013,22(6):554-559.
[5]Garabed Eknoyan,Bertram L.Kasiske,David C.Wheeler,et al.KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis,Evaluation,Prevention,and Treatment of Chronic KidneyDisease-Mineral and Bone Disorder(CKD-MBD)[J].Kidney Int,2017,7(Suppl):35-36.
[6]卢永欣,梁敏.帕立骨化醇在慢性肾脏病患者中的应用[J].临床肾脏病杂志,2015,15(9):571-574.
[7]云扬,张晨,李德天,等.帕立骨化醇对维持性血液透析患者炎症状态及氧化应激的影响[J].中国血液净化,2018,17(10):677-681.
[8]Ketteler M,Martin KJ,Wolf M,et al.Paricalcitol vs.cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis:result of the IMPACT SHPTstudy[J].Nephrol Dial Transplant,2012,27:3270-3278.
[9]Yucheng Yan,Jiaqi Qian,Nan Chen,et al.Efficacy and initial dose determination of paricalcitol for treatment of secondary hyperparathyroidism in Chinese subjects[J].Clin Nephrol,2014,81(1):20-29.
[10]张玉梅,宋鲁平.康复评定常用量表[M].北京.科学技术文献出版社,2018:464-465.
[11]Biggar P,Kovarik J,Klauser-Braun R,et al.Paricalcitol Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients:A German-Austrian,Single-Arm,OpenLabel,Prospective,Noninterventional,Observational Study[J].Nephron Clin Pract,2014,126:39-50.
[12]Ketteler M,Martin KJ,Cozzolino M,et al.Paricalcitol versus cinacalcet plus low-dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis:study design and baseline characteristics of the IMPACT SHPT study[J].Nephrol Dial Transplant,2012,27(5):1942-1949.
[13]王泰娜,徐斌,刘志红,等.帕立骨化醇治疗血液透析患者伴继发性甲状旁腺功能亢进[J].肾脏病与透析肾移植杂志,2015,24(1):1-5.
[14]郝娟,程叙扬,左力,等.帕立骨化醇不同给药方式治疗继发性甲状旁腺功能亢进症的对照研究[J].中国血液净化,2015,14(9):540-544.