慢性肾脏病继发性甲旁亢治疗进展（综述）

继发性甲状旁腺功能亢进症(SHPT)是慢性肾脏病(CKD)常见的并发症。近年研究发现,新型的磷结合剂碳酸镧,能有效降低血清磷水平,并不引起继发骨损害和高钙血症,是一种相对较安全的磷结合剂,西那卡塞是被称为拟钙剂(calcimimetics)的新一类化合物中的第一个药物,能激活甲状旁腺中的钙受体,从而降低甲状旁腺素的分泌。尤其适用于慢性肾衰竭患者顽固性、继发性甲状旁腺功能亢进伴有高磷血症的短期治疗。     

西那卡塞联合骨化三醇注射液治疗维持性血液透析患者中重度继发性甲状旁腺功能亢进的效果观察

目的观察西那卡塞联合骨化三醇注射液治疗维持性血液透析(maintenance hemodialysis,MHD)患者中重度继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)的效果及安全性。方法选择2017年1月—2020年1月在我院血液透析室行MHD治疗的中重度SHPT患者48例,根据治疗方法不同分为观察组与对照组各24例。对照组予骨化三醇注射液治疗,观察组在上述治疗基础上加用西那卡塞治疗。连续治疗6个月后,观察两组血全段甲状旁腺激素(iPTH)、钙(Ca)、磷(P)、碱性磷酸酶(ALP)、β-Ⅰ型胶原C-末端肽(β-CTX)、Ⅰ型前胶原N-端前肽(PⅠNP)变化和iPTH、Ca、P达标情况及甲状旁腺体积,并观察两组治疗期间不良反应发生情况。结果治疗后对照组血Ca较治疗前升高(P<0.05),观察组血Ca无明显变化(P>0.05);治疗后两组血P、iPTH、ALP、β-CTX及PⅠNP较治疗前明显下降(P<0.01);治疗后观察组较对照组血Ca、P、iPTH、ALP、β-CTX及PⅠNP下降明显,差异有统计学意义(P<0.05或P<0.01)。治疗后观察组iPTH、Ca、P达标率明显高于对照组(P<0.05)。治疗后,对照组甲状旁腺体积无明显变化(P>0.05),观察组甲状旁腺体积缩小(P<0.01),且观察组甲状旁腺体积小于对照组(P<0.01)。两组治疗期间不良反应比较差异无统计学意义(χ^2=0.105,P=0.745)。结论西那卡塞联合骨化三醇注射液治疗MHD患者中重度SHPT效果显著,可降低血清iPTH水平及改善钙磷代谢紊乱和骨代谢异常,缩小甲状腺体积,且安全性好。     

西那卡塞联合骨化三醇对血液透析继发性甲状旁腺功能亢进患者的疗效观察

目的 探讨西那卡塞联合骨化三醇对血液透析继发性甲状旁腺功能亢进患者的疗效。方法 选取2017年1月～2019年1月在我院行血液透析继发性甲状旁腺功能亢进患者64例,随机分为观察组与对照组各32例。两组患者继续予以维持性透析治疗,对照组予以骨化三醇治疗,观察组在此治疗基础上加西那卡塞治疗。两组均连用3个月,检测两组治疗前后血清钙、血清磷、全段甲状旁腺激素水平及甲状旁腺体积,并评估其临床疗效及不良反应。结果 治疗3个月后两组血清磷与全段甲状旁腺激素水平均较前明显下降,血清钙水平均较前明显升高(P0.05或P0.01),且观察组变化幅度较对照组更显著(P0.05);两组甲状旁腺长、宽、厚及体积均较前明显下降(P0.05或P0.01),且观察组下降幅度较对照组更显著(P0.05)。观察组临床治疗总有效率明显高于对照组(χ~2=4.272,P0.05)。观察组和对照组不良反应发生率分别为12.50%(4/32)和6.25%(2/32),症状均较轻,两组比较差异无统计学意义(χ~2=0.180,P0.05)。结论 西那卡塞联合骨化三醇治疗血液透析继发性甲状旁腺功能亢进患者的临床效果确切,安全性较好,能明显降低甲状旁腺激素水平及甲状旁腺体积,改善钙磷代谢紊乱。     

Cinacalcet sustainedly prevents pancreatitis in a child with a compound heterozygous SPINK1/AP2S1 mutation

Familial hypocalciuric hypercalcemia is an autosomal dominant genetic disorder characterized by hypercalcemia associated with inappropriate hypocalciuria and normal parathyroid hormone levels.Acute recurrent pancreatitis (ARP) is rare in children. Predisposing factors include hypercalcemia and mutations in the serine protease inhibitor Kazal-type 1 (SPINK1) gene. The disease carries a heavy morbidity and preventive treatment options are scant.Here, we report a child with a novel genetic/metabolic form of ARP associated with compound heterozygous SPINK1/AP2S1 (adaptor protein-2 σ1-subunit) mutations, recurrence of which was completely abrogated for 6 years by cinacalcet treatment.     

静态顶空气相色谱法测定盐酸西那卡塞中的残留溶剂

目的 采用静态顶空气相色谱分析方法测定盐酸西那卡塞原料药中残留的四氢呋喃、乙酸乙酯、二氯甲烷、乙醇和甲苯.方法 采用DB-WAX色谱柱(30 m×0.32 mm,0.25 μm),FID检测器,内标法定量.分别考察了溶剂、顶空平衡温度、顶空平衡时间、相比、色谱柱对残留溶剂测定的影响.结果 5种残留溶剂的线性范围分别为36 ～ 108、250 ～ 750、30 ～ 90、250 ～750、44.5 ～133.5μg·mL-1,平均回收率分别为98.2％、98.3％、98.4％、98.8％、98.1％,RSD分别为3.37％、3.36％、4.65％、2.97％、3.13％.结论 所用方法简便、准确、灵敏度高、重复性好,适用于盐酸西那卡塞中残留溶剂的测定.     

西那卡塞对维持性血液透析继发性甲状旁腺功能亢进患者FGF-23的影响

目的 研究西那卡塞对维持性血液透析继发性甲状旁腺功能亢进患者FGF-23的影响。方法 选取2015年1月~2016年10月在天津市第一中心医院血液净化中心行维持性血液透析治疗合并继发性甲状旁腺功能亢进的患者,按入院顺序随机分为观察组及对照组,对照组40例,给予骨化三醇治疗,观察组39例,给予对照组患者相同的骨化三醇治疗的基础上,再加用盐酸西那卡塞片,两组均连续治疗3个月。监测两组治疗前后的尿素氮、血肌酐、KT/V、血清钙、血清磷、碱性磷酸酶、钙磷乘积、全段甲状旁腺激素 (iPTH)及血清FGF-23。结果 治疗后,两组患者的BUN、SCr和Kt/V 较治疗前,差异无统计学意义（P＞0.05）;血清钙观察组治疗后低于对照组（P＜0.05）,对照组治疗前后,差异无统计学意义（P＞0.05）;两组血清磷、ALP、钙磷乘积、iPTH、FGF-23治疗后降低,且治疗后观察组优于对照组,差异有统计学意义 (P<0.05)。结论 西那卡塞对于维持性血液透析合并继发性甲状旁腺功能亢进的患者能够降低甲状旁腺激素及FGF-23水平,缩小甲状旁腺体积。     

继发性甲状旁腺功能亢进的治疗策略

继发性甲状旁腺功能亢进(SHPT)已成为慢性肾脏病(CKD)常见的并发症之一,严重影响患者生活质量。其治疗策略包括药物、手术和介入。药物包括非选择性和选择性活性维生素D、拟钙剂(西那卡塞),药物治疗期间强调动态观察血清全段甲状旁腺激素(iPTH)和血清钙、磷的变化,以及时调整药物剂量。药物治疗无效且具备手术指征者,可考虑甲状旁腺切除手术(PTX)或超声介入治疗。PTX前需要高频彩超和(或)⁹⁹Tc^m-MIBI双时相显像用于甲状旁腺的定位诊断。PTX有三种术式,其中甲状旁腺全切除加移植是目前最常用的术式。对于不能耐受手术和需要再次PTX的患者可以选择一种新的治疗策略,即彩色超声介导下甲状旁腺热消融术。     

Association of nodular hyperplasia with resistance to cinacalcet therapy for secondary hyperparathyroidism in hemodialysis patients

There have been few long-term prospective studies investigating the effect of cinacalcet on secondary hyperparathyroidism with or without nodular hyperplasia. We examined whether the effect of cinacalcet on secondary hyperparathyroidism differed between patients with or without nodular hyperplasia. Stable hemodialysis patients with secondary hyperparathyroidism resistant to conventional treatment received cinacalcet for 12 months. Based on ultrasonography findings, patients were divided into group S (gland < 500 mm(3) without nodular hyperplasia) and group L (gland ≥ 500 mm(3) with nodular hyperplasia). Serum levels of intact parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin, and cross-linked N-terminal telopeptide of type 1 collagen were measured. Thirty-one patients completed the study. The changes of parameters from the baseline did not differ significantly between the two groups after 6 months. However, the percentage reduction of each parameter was significantly smaller in group L compared with group S after 12 months. Nodular hyperplasia is associated with resistance to cinacalcet therapy in patients on chronic dialysis with secondary hyperparathyroidism.     

Parathyroid Gland Ultrasound Patterns and Biochemical Findings After One-year Cinacalcet Treatment for Advanced Secondary Hyperparathyroidism

Cinacalcet efficacy is limited in severe secondary hyperparathyroidism (SHPT) and its effect on parathyroid gland (PTG) volume and morphology have not been sufficiently investigated. We evaluated the effect of cinacalcet treatment for one year on the laboratory parameters of calcium–phosphorus metabolism and PTG ultrasound (US) patterns in hemodialysis (HD) patients with severe SHPT and US results indicative of nodular hyperplasia. Thirteen HD patients with severe SHPT (intact parathyroid hormone >700 pg/mL), US/scintigraphic evidence of at least one PTG with a diameter >7 mm, and high surgical risk or refusal of surgery were included. The patients were treated with cinacalcet. The initial dose of 30 mg was increased up to 180 mg once daily. At baseline and after one year of cinacalcet treatment a neck US was performed, providing data on 22 parathyroid glands in eight patients. The mean diameter at baseline and at one year was 12.6 ± 5.9 and 13.0 ± 5.3 mm, respectively (P = 0.46). Similarly, the mean volume at baseline and at one year was 513.4 ± 416.3 and 556.8 ± 480.8 mm³, respectively (P = 0.18). The US structural score remained unchanged in 16 parathyroid glands and increased in 6 (P < 0.03), while the vascular score remained unchanged in 16 parathyroid glands and decreased in 6 (P = 0.25). Thus it can be concluded that cinacalcet treatment for one year in HD patients with severe SHPT is not associated with significant changes in parathyroid gland US patterns.