帕立骨化醇联合西那卡塞治疗血液透析伴继发性甲状旁腺功能亢进的效果研究

目的:研究帕立骨化醇联合西那卡塞治疗维持性血液透析(MHD)继发性甲状旁腺功能亢进(SHPT)患者的疗效和安全性。方法:选取2019年8月至2020年8月本院血液净化中心收治的22例MHD伴SHPT患者为研究对象,所有患者根据全段甲状旁腺激素(iPTH)水平予以帕立骨化醇联合西那卡塞治疗。分别于治疗前及治疗后2、4、8...     

西那卡塞联合小剂量骨化三醇治疗维持性血液透析合并继发性甲状旁腺功能亢进的疗效观察

目的:探讨西那卡塞联合小剂量骨化三醇治疗维持性血液透析(MHD)合并继发性甲状旁腺功能亢进(SHPT)的疗效观察。方法:选取本院肾病中心2012年8月至2017年8月收治的80例MHD合并SHPT患者,采用随机数字表法将其分为骨化三醇组和联合治疗组,每组各40例。骨化三醇组采用骨化三醇治疗,联合治疗组采用西那卡塞联合小...     

Gallstones were associated with the gastrointestinal adverse events of cinacalcet in hemodialysis patients with secondary hyperparathyroidism

This study aimed to investigate the association of gastrointestinal (GI) adverse events of cinacalcet with gallstones in the hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). A total of 23?HD patients under the treatment with cinacalcet and 101 control patients were enrolled in this cross-sectional study. We investigated the prevalence of gallstones and the association of GI adverse events of cinacalcet with gallstones. The prevalence of gallstones was significantly higher in the HD patients with cinacalcet compared with the controls (47.8% vs. 15.8%). The longer time on HD, hypercalcemia, hyperphosphatemia and elevated parathyroid hormone level were observed in the HD patients with cinacalcet. Besides, GI adverse events of cinacalcet were observed more frequently in the HD patients with gallstones compared with those without gallstones (odds ratio 13.5, 95% CI: 1.80–101). Therefore, screening for gallstones before dosing cinacalcet may reduce the risk of GI adverse events in SHPT patients.     

帕立骨化醇治疗维持性血液透析患者继发性甲状旁腺功能亢进症的前瞻性研究

目的 观察帕立骨化醇治疗维持性血液透析患者继发性甲状旁腺功能亢进症（secondary hyperparathyroidism,SHPT）的疗效及安全性.方法 选择我科血液净化中心进行维持性血液透析治疗的13例患者,血全段甲状旁腺素（intact parathyroid hormone,iPTH）≥33 pmol/L,血钙水平＜2.55 mmol/L,钙磷乘积＜65,根据iPTH水平使用帕立骨化醇1～18 μg治疗,于每次透析治疗后给药,共观察12周.分别于治疗前及治疗后第2、4、6、8、10、12周测定患者的iPTH、血钙、血磷水平.结果 13例患者的血清iPTH水平在治疗后第2、4周已开始下降,但与治疗前相比差异无统计学意义.从治疗后第6周开始,iPTH水平与治疗前相比存在统计学差异（P＜0.05）,治疗后第12周时下降至（46.68±38.06） pmol/L,与治疗前（78.30±52.13） pmol/L比较,有统计学差异（P＜0.01）.治疗后第2、4周血钙水平升高,与治疗前比较有统计学差异（P＜0.05）,其中治疗后第4周时血钙水平升高尤为显著（P＜0.01）.经调整帕立骨化醇剂量后,治疗后第6周患者的血钙水平逐渐恢复正常并保持稳定,血磷、钙磷乘积水平在治疗前、后均无明显统计学差异.治疗过程中,患者耐受性良好,无相关不良反应的发生.结论 使用帕立骨化醇治疗维持性血液透析患者SHPT是有效、安全的.     

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。     

唑来膦酸治疗血液透析患者继发性甲状旁腺功能亢进合并骨质疏松的疗效分析

目的评价唑来膦酸注射液治疗维持性血液透析患者继发性甲状旁腺功能亢进合并骨质疏松的临床疗效及安全性。方法回顾性分析2013~2014年在我院行维持性血液透析治疗的继发性甲状旁腺功能亢进合并骨质疏松的患者8例,给予唑来膦酸注射液治疗,观察治疗前、治疗后6个月和12个月的血清全段甲状旁腺激素(intact parathyroid hormone,iPTH)、钙、磷、碱性磷酸酶、白细胞、血小板水平的变化情况。测量治疗前及治疗12月后患者腰椎、左右侧股骨颈的骨密度,记录用药后不良反应及患者临床症状改善情况。结果与治疗前比较,治疗6月及12月后血清iPTH、钙明显下降,差异有统计学意义;治疗后6个月与治疗12月后相比,血清iPTH、钙水平虽有所下降,但差异无统计学意义。血清磷、碱性磷酸酶等指标与治疗前相比,有下降趋势,但差异无统计学意义。唑来膦酸治疗12个月后,患者腰椎、左右股骨颈骨密度均有不同程度的增高,差异有统计学意义。用药后有1例患者出现肌肉关节酸痛,对症处理后其症状缓解;1例患者血小板轻度降低,其余尚未观察到其他不良反应,可能与研究病例数较少有关;3例患者自觉骨痛症状较前缓解。结论唑来膦酸注射液可有效降低维持性血液透析继发性甲状旁腺功能亢进合并骨质疏松患者的血iPTH、血清钙水平,增加骨密度,缓解骨痛症状,且安全性好。     

帕立骨化醇治疗维持性血液透析患者继发性甲状旁腺机能亢进症的效果

目的:探讨帕立骨化醇治疗维持性血液透析患者继发性甲状旁腺机能亢进症的效果。方法:筛选2021年5月至2021年8月首都医科大学附属北京朝阳医院血液净化科收治的维持性血液透析继发性甲状旁腺机能亢进症患者20例(全段甲状旁腺素500~2 000 pg/ml),予帕立骨化醇治疗,每次5 μg,每周3次,后续根据血清全段甲状旁...     

西那卡塞治疗慢性肾脏疾病透析患者继发性甲状旁腺功能亢进症安全性与有效性的Meta分析

目的：综合分析西那卡塞治疗慢性肾脏疾病合并继发性甲状旁腺功能亢进症（second-ary hyperparathyroidism,SHPT）患者的安全性与有效性。方法在 Cochrane Central Register of Controlled Trials,Cochrane Database of Systematic Reviews,Embase,Medline四个数据库中检索应用西那卡塞治疗慢性肾脏疾病合并 SHPT 患者的随机对照分析。其纳入标准为慢性肾脏疾病合并SHPT且正在行透析治疗的患者,年龄≥18岁;治疗组接受西那卡塞加常规治疗,对照组接受安慰剂加常规治疗或只接受常规治疗,常规治疗包括维生素D类似物和（或）磷结合剂。结果共检索出14篇满足纳入标准的文献。结果显示西那卡塞明显降低了 SHPT患者血甲状旁腺素（parathyroid hor-mone,PTH）水平[MD,-285.89 ng/L （95% CI：-341.27,-230.51）]、血钙浓度[MD,-0.21 mmol/L（95% CI：-0.24,-0.18）]、血磷浓度[MD,-0.13 mmol/L（95% CI：-0.17,-0.08）]以及钙磷乘积的水平[MD,-8.99（95% CI：-10.37,-7.61）],但是西那卡塞对骨代谢方面作用不确定,也并不能降低患者的全因病死率[RR 0.97（95% CI：0.89,1.05）]。与对照组比较,使用西那卡塞治疗的患者更容易发生低钙血症、恶心、呕吐、上呼吸道感染。结论西那卡塞治疗能有效的改善SHPT患者血生化指标,但并没有有效降低患者的全因病死率。     

Efficacy and safety of cinacalcet for the treatment of secondary hyperparathyroidism in patients with advanced chronic kidney disease before initiation of regular dialysis

Aim: To evaluate the compassionate use of cinacalcet for the management of secondary hyperparathyroidism in patients who are not on dialysis. Methods: Patients with stage 4–5 chronic kidney disease (CKD) who were not on dialysis, had an intact parathyroid hormone (iPTH) level greater than 300 pg/mL, and had not responded satisfactorily to treatment with phosphate binders and vitamin D were prospectively studied. Patients received 6 months of compassionate treatment with cinacalcet, which was initiated at a dose of 30 mg/day orally and flexibly dosed thereafter based on iPTH levels. Results: Twenty‐six patients with a mean age ± standard deviation (SD) of 58.8 ± 16.1 years were enrolled in the study and included in the statistical analysis. The mean percentage change in iPTH levels from baseline after 6 months of treatment was ?67.9 ± 17.0%, with 92.3% (95% confidence interval (CI), 75.9–97.9) of patients showing an iPTH level within the limits recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. The mean serum calcium concentrations had decreased significantly at the end of the study (?8.0 ± 6.9%), while the mean serum phosphorus concentration had significantly increased (+8.3 ± 17.0%). Conclusion: Our results suggest that cinacalcet may be a useful alternative for the treatment of secondary hyperparathyroidism in pre‐dialysis patients who are unresponsive to other treatments. The hypocalcemia and hyperphosphatemia reported in previous studies may not occur if a moderate dose of calcimimetics is used in patients with marginal glomerular filtration rates, especially if combined with vitamin D analogues and calcium‐based phosphate binders.     

Evolution of secondary hyperparathyroidism in patients following return to hemodialysis after kidney transplant failure

IntroductionSevere uncontrolled secondary hyperparathyroidism and kidney transplantation history are both risk factors for fractures in hemodialyzed patients. Moreover, patients who return to dialysis after transplant failure have more severe infections/anemia and higher mortality risk than transplant-naive patients starting dialysis with native kidneys. In this context, our aim was to test the hypothesis that transplant failure patients have more secondary hyperparathyroidism than transplant-naive patients.MethodsWe retrospectively compared 29 transplant failure patients to 58 transplant-naive patients matched for age, sex, chronic kidney disease duration and diabetes condition (1 transplant failure/2 transplant-naive ratio), who started dialysis between 2010 and 2014. Clinical and biological data were collected at baseline, 6 and 12 months.FindingsAt baseline, neither serum parathyroid hormone (transplant-naive: 386 ± 286 pg/mL; transplant failure: 547 ± 652 pg/mL) nor serum 25-hydroxyvitamin D (transplant-naive: 27.8 ± 17.0 μg/L, transplant failure: 31.1 ± 14.9 μg/L) differed between groups. However, serum parathyroid hormone at 12 months and the proportion of patients with uncontrolled secondary hyperparathyroidism (parathyroid hormone > 540 pg/mL, KDIGO criteria) were significantly higher in transplant failure than in transplant-naive (parathyroid hormone: 286 ± 205 vs. 462 ± 449, P < 0.01; uncontrolled secondary hyperparathyroidism: 30% vs. 13%, P < 0.01, respectively). Within the transplant failure group, patients with uncontrolled secondary hyperparathyroidism at 12 months were younger than patients with normal or low parathyroid hormone.DiscussionThis retrospective and monocentric study suggests that transplant failure patients are more likely to develop secondary hyperparathyroidism. Thus, finding high serum parathyroid hormone in young transplant failure patients, who are expected to undergo further transplantations, should incite physicians to treat early and more aggressively this complication.     

慢性肾功能衰竭继发甲状旁腺功能亢进的外科治疗

目的：探讨甲状旁腺全切除加前臂自体移植术治疗继发性甲状旁腺功能亢进的疗效。方法：1999年11 月～2005年4月，对15例继发性甲状旁腺功能亢进病人施行了上述治疗。结果：15例患者共切除增生性甲状旁腺52 枚。B 超对甲状旁腺的检出率为96． 2%。术后临床症状改善，血钙控制在正常范围内，术后第1天、1周、2周、3周和 3个月血全段甲状旁腺素(intact parathyroid hormone，iPTH)平均值分别为14． 0、 17． 8、 113． 7、 145． 0和148． 2ng/L。1例 术后4年移植物增生复发，切除后临床症状改善，无并发症。结论：甲状旁腺全切除加前臂自体移植术治疗继发性 甲状旁腺功能亢进是可行的，手术安全，近期疗效满意，其远期疗效有待进一步随访加以肯定。     

司维拉姆联合西那卡塞治疗血液透析并发继发性甲状旁腺功能亢进患者的疗效观察和对成纤维生长因子23的影响

目的:观察司维拉姆联合西那卡塞对维持性血液透析并发继发性甲状旁腺功能亢进患者的疗效及对成纤维细胞生长因子23(FGF-23)和钙、磷的影响。方法:选取2017年4月至2018年10月在本院收治的并发继发性甲状旁腺功能亢进[甲状旁腺激素(iPTH)>300 pg/mL]的维持性血液透析患者110例,随机将患者分为碳酸司维...     

Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis

This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (IV) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (2°HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values >400 pg mL^–1, calcium levels 10.5 mg dL^–1 and calcium×phosphorus product values 70 mg² dL^–2 were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5–1.5 g) were based on the severity of 2ºHPT. The dose was increased every two weeks by 0.25 g until there was at least a 30% decrease in PTH from baseline, or Ca>11.0 mg dL^–1, or Ca×P>75 mg² dL^–2. Overall, 11/21 (52%) patients in the calcitriol group had two consecutive 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L^–1 in the calcitriol group and increased from 547 to 669 IU L^–1 in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 g L^–1 in the calcitriol group and increased from 105.3 to 148.5 g L^–1 in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium×phosphorus (Ca×P>75 mg² dL^–2) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus >6.5 mg dL^–1 occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels >10.5 mg dL^–1 were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that IV calcitriol, at initial doses of 0.5–1.5 g, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca×P product.     

Risk factors for hypocalcemia in dialysis patients with refractory secondary hyperparathyroidism after parathyroidectomy: a meta-analysis

ObjectiveHypocalcemia after parathyroidectomy (PTX) results in tetany, diarrhea, cardiac arrhythmia, and even sudden death. However, a meta-analysis or systematic evaluation of risk factors with the occurrence and development of hypocalcemia in patients with secondary hyperparathyroidism (SHPT) after PTX has never been performed.MethodsA thorough search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and EMBASE, was performed to retrieve relevant studies from database inception to June 2021. Quality of the included studies was assessed by two independent reviewers using the Newcastle–Ottawa Scale. Review Manager 5.3 and Stata 16.0 were used for meta-analysis. The random-effects model was adopted to calculate the 95% CIs (I²> 50% or p < 0.05) of the combined effect size and the corresponding homogeneous data. Otherwise, a fixed-effects model was used.ResultsThirteen studies including 2990 participants who met the inclusion criteria were enrolled in the present meta-analysis. The overall quality of the enrolled studies had a score of >7 points. Risk factors significantly related to hypocalcemia in patients with SHPT after PTX were preoperative serum calcium (OR 0.19, 95%CI 0.11–0.31), preoperative alkaline phosphatase (ALP) (OR 1.01, 95% CI 1.01–1.02), and preoperative intact parathyroid hormone (iPTH) (OR 1.38, 95%CI 1.20–1.58). Meanwhile, age (OR 0.97, 95%CI 0.87–1.10) was not significantly correlated with hypocalcemia after PTX.ConclusionsBased on the current evidence, preoperative serum calcium, preoperative ALP, and preoperative iPTH were significant predictors of hypocalcemia in patients with SHPT after PTX. More attention should be given to patients with these risk factors for the prevention of postoperative hypocalcemia.     

高危尿毒症患者每日短时透析的临床初步经验

目的观察高危尿毒症患者应用每日短时透析的疗效。方法16例常规血液透析(HD)治疗无效或不能耐受HD的高危尿毒症患者改作每周6次、每次2h的血液透析滤过或血液滤过治疗,随访8周。比较每日透析治疗前后患者的透析不良反应、血压、体重变化、每周Kt/V,血清磷、血清白蛋白、血红蛋白、心胸比率、左心重量指数以及SF-36生活质量评价的变化。结果与常规透析比较,患者每周Kt/V从4.36±0.62升高至4.88±0.41(P=0.009),血压下降至趋于正常,透析中低血压反应明显减少,血清白蛋白明显升高,血清磷明显下降,血红蛋白明显升高,心脏缩小(P均<0.05),SF-36生活质量评分明显改善。结论高危尿毒症患者应用每日透析治疗后耐受性良好,并能使血压平稳,透析充分,更好地预防透析骨病,改善患者营养状况,减少及治疗心血管并发症,提高生活质量。     

腔镜下与开放手术治疗继发性甲状旁腺功能亢进的临床比较

目的:探讨腔镜下甲状旁腺全切(ETP)+部分甲状旁腺组织前臂移植(PTA)与开放甲状旁腺全切术(OP)+PTA治疗继发性甲状旁腺功能亢进(SHPT)的临床比较。方法:2009年4月—2012年6月22例SHPT患者经胸前路径行ETP,同时将16枚1 mm×1 mm×3 mm大小的增生甲状旁腺部分组织移植于患者前臂肱桡侧肌膜下。同期25例SHPT患者经颈部行OP+PTA。结果:22例ETP+PTA及25例OP+PTA均顺利完成,无术中及围手术期死亡。ETP+PTA患者手术时间、出血量、下床时间、住院时间较OP+PTA患者明显减少(P0.05),ETP+PTA组术中、术后并发症与OP+PTA组差异无统计学意义(P0.05),而术后临床症状均有明显改善,生化检查均恢复正常或明显改善,寻找甲状旁腺个数ETP+PTA组亦优于OP+PTA组(P0.05),随访6个月复发率差异无统计学意义(P0.05)。结论:ETP+PTA操作安全,寻找甲状旁腺更有优势,喉返神经的保护更好,出血量更少,同时具有美容效果,是对传统手术的改进和发展,值得推广。     

甲状旁腺全切＋自体移植术治疗继发性甲状旁腺功能亢进症疗效分析

目的探讨甲状旁腺全切＋自体移植术(tPTX＋AT)治疗维持性血液透析患者继发性甲状旁腺功能亢进症(SHPT)的有效性、安全性以及术后低钙的危险因素。 方法纳入我院2013年1月至2016年11月因SHPT行tPTX＋AT手术的维持性血液透析患者93例,收集术前术后症状、血钙、磷、碱性磷酸酶(ALP)、全段甲状旁腺激素(iPTH)、病理类型、并发症等临床资料。依据术后24 h血钙水平分为正常血钙组(Ca≥2.11 mmol/L)及低钙血症组(Ca<2.11 mmol/L),应用单因素分析及逐步Logistic回归分析术后早期低钙血症的危险因素。 结果手术成功率92.5%。切除360枚甲状旁腺腺体,异位甲状旁腺10枚。病理结果多为腺瘤样增生(96.4%)。同术前相比,术后血清iPTH、磷、ALP明显下降(P<0.05)。低钙血症是术后最常见并发症,发生率82.8%,血钙水平与术前血钙、年龄正相关(r＝0.300, P<0.01;r＝0.265, P<0.01),与术前iPTH、ALP水平负相关(r＝－0.461, P<0.01;r＝－0.477, P<0.01)。术前低血钙(OR＝0.113, P＝0.045)、高ALP水平(OR＝1.050, P<0.001)、高iPTH水平(OR＝1.002, P＝0.004)是术后早期低钙血症发生的独立危险因素。 结论tPTX＋AT可以安全、有效、快速的降低维持性血液透析患者血清iPTH水平,改善机体的钙磷代谢紊乱,但需重视并积极纠正术后低钙血症。针对存在术前低血钙、高iPTH及高ALP水平等高危因素的患者,术前积极纠正低钙血症可能是预防术后低钙的有效干预方式。     

Use of calcimimetics in uremic patients with secondary hyperparathyroidism: review

Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The activation of this receptor by small changes in extracellular ionized calcium (ec(Ca2+)) regulates PTH, calcitonin secretion, urinary calcium excretion, and ultimately, bone turnover. The cloning of this CaR and the discovery of mutations making the receptor less or more sensitive to calcium allowed a better understanding of several hereditary disorders characterized either by hyperparathyroidism or hypoparathyroidism. This CaR became an ideal target for the development of compounds, the calcimimetics, able to amplify the sensitivity of the CaR to ec(Ca2+) suppressing PTH levels with a resultant fall in blood Ca2+. The first clinical studies with first-generation calcimimetic agents have demonstrated their efficacy lowering plasma intact PTH concentration in uremic patients with secondary hyperparathyroidism. However, the low bioavailability of these first calcimimetics predicts a difficult clinical utilization. The second-generation calcimimetic AMG-073, with a better pharmacokinetic profile, appears to be effective and safe for the treatment of secondary hyperparathyroidism, producing suppression of PTH levels with a simultaneous reduction in serum phosphorus levels and the calcium X phosphorus product. The advantage of controlling PTH secretion without the complications related to hypercalcemia, hyperphosphatemia, and increased calcium X phosphorus product is very promising.     

Elderly patients on chronic hemodialysis: Effect of the secondary hyperparathyroidism on the hemoglobin level

In patients on chronic hemodialysis (CHD)hyperparathyroidism (HPTH) is associated withanemia and resistance to erythropoietin (EPO). This study included 86 CHD elderly pts (meanage 74.8 y, mean time on CHD = 50.5 mos); theywere divided into two groups: I (n = 31) – PTH> 250 pg/mL and II (n = 55) – PTH < 250 pg/mL.All these patients had been on CHD for> 6 mos. No differences were found betweengroups in respect to age, sex distribution andtime on CHD. The levels of creatinine, BUN, Ca,Al, Fe, albumin and ferritin were similar.Group I had a higher P level (5.4 vs 4.3 mg/dL,p = 0.001) and Ca x P (53.5 vs 43.7, p =0.009). Also the Hct (31 vs 33.5%, p = 0.008)and the Hb (10.4 vs 11.2 g/dL, p = 0.009) values werelower in Group I. The EPO dose (88 vs 85 U/kg/week,p = ns) was similar in the two groups.Our data showed that elderly patients with HPTHhave lower Hct and Hb levels than do youngerpatients on a similar EPO dose. We believethese patients will need a more aggressivetherapy with calcitriol.