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...     

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...     

西那卡塞治疗血液透析患者继发性甲状旁腺功能亢进7例分析

目的：观察西那卡塞对血液透析患者继发性甲状旁腺功能亢进（SHPT）的治疗作用。方法：收集7例西那卡塞治疗的血液透析患者资料,观察其一般情况、检测血清钙、磷、全段甲状旁腺激素（i PTH）等指标。结果：7例患者中有2例为甲状旁腺切除术后复发的,有4例在用药时已有甲状旁腺结节形成,西那卡塞的平均有效剂量为50 mg/d,用药1~3个月后血清钙（2.567 vs 2.136）及i PTH（1 847 vs 623）均有显著的下降（P〈0.05）,尚未观察到血清磷有明显变化。结论：西那卡塞可有效治疗血液透析患者的SHPT,因其具有降低血钙的作用,尤其适用于伴有高钙血症者。     

西那卡塞治疗肾移植术后三发性甲状旁腺功能亢进2例

临床资料 例1 ,男,41岁,2008年8月因慢性肾功能不全尿毒症期行血液透析治疗,每周3次.术前血清全段甲状旁腺激素(intact parathyroid hormone ,iPT H )3500 ng/L.胸部CT:主动脉弓、左右冠状动脉钙化.2017年9月29日在湘雅二医院行同种异体肾移植术,术后免疫方案:他克莫...     

西那卡塞联合活性维生素D治疗终末期肾病透析患者继发性甲状旁腺功能亢进症疗效及安全性的Meta分析

目的评价西那卡塞联合活性维生素D治疗终末期肾病(ESRD)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。方法计算机检索Pubmed、Embase、Cochrane图书馆临床对照试验资料库,搜索所有西那卡塞联合活性维生素D治疗ESRD透析患者SHPT的随机对照试验,检索时限为建库至2018年12月31日。采用RevMan 5.3软件进行Meta分析。结果共纳入8项随机对照研究,包括2 169例患者。Meta分析结果显示,与单用活性维生素D相比,西那卡塞联合活性维生素D治疗组明显降低了透析患者血浆甲状旁腺激素水平[RR=4.66,95%CI(2.27,9.55),P0.01]、血钙浓度[MD=-0.81,95%CI(-0.92,-0.69),P0.01]、血磷浓度[MD=-0.46,95%CI(-0.65,-0.26),P0.01]及钙磷乘积[MD=-9.86,95%CI(-12.54,-7.19),P0.01];而西那卡塞联合活性维生素D治疗对不良反应发生率[RR=1.21,95%CI(0.82,1.77),P=0.33]及全因死亡率[RR=0.90,95%CI(0.54,1.48),P=0.67]无显著影响。结论西那卡塞联合活性维生素D治疗ESRD透析患者SHPT的疗效优于单用活性维生素D,且不增加不良反应发生率,但并不能降低全因死亡率。     

成纤维细胞生长因子23在继发性甲状旁腺功能亢进症中的作用

目的 研究成纤维细胞生长因子23（FGF23）在继发性甲状旁腺功能亢进症（SHPT）中的作用。 方法 （1）收集38例维持性血液透析（MHD）患者血清,用ELISA法检测FGF23和化学发光酶免疫分析法检测全段甲状旁腺激素（iPTH）。（2）6例行甲状旁腺全切除（PTX）加自体前臂移植术的SHPT患者,取其甲状旁腺组织行细胞培养。培养24 h后用0.1 mg/L的FGF23分别刺激0、6、12、24、48 h时收集上清液检测iPTH。（3）取33例严重SHPT患者和3例健康人的甲状旁腺组织,用免疫组化SP法检测成纤维细胞生长因子受体（FGFR）1、FGFR3、转录因子GATA-3、增殖细胞核抗原（PCNA）及PV法检测Klotho的表达,计算阳性细胞率或积分吸光度。 结果 (1)MHD患者血清FGF23[（3901.85±2618.11） ng/L]与iPTH[（460.00±489.77） ng/L]呈正相关（r2 = 0.3009,P = 0.0004）。(2)FGF23仅在刺激24 h时,才有抑制iPTH的作用（P ＜ 0.05）,其它时段均无抑制作用。(3)SHPT患者甲状旁腺PCNA、 GATA-3、 FGFR3、 Klotho表达均显著高于健康人,而FGFR1表达显著低于健康人。(4)GATA-3阳性细胞率与血清iPTH水平及PCNA阳性细胞率均呈正相关（r2 = 0.1901,P = 0.0425;r2 = 0.2584,P = 0.0025）。Klotho表达与FGFR1和FGFR3表达呈正相关（r2 = 0.2046,P = 0.0082;r2 = 0.2833,P = 0.0014）。PCNA表达与FGFR1表达呈负相关（r2 = 0.1292,P = 0.0399);与FGFR3表达呈正相关（r2 = 0.1226,P = 0.0457）。FGFR1表达和血清磷水平呈负相关（r2 = 0.2329,P =0.0044）;与血清钙水平呈正相关（r2 = 0.1422,P = 0.0305）。 结论 MHD患者iPTH水平与FGF23水平呈正相关。FGF23能抑制iPTH分泌,但作用弱且短。这可能与GATA-3、甲状旁腺细胞增殖、FGFR3表达增多,FGRF1表达下降有关。     

成纤维生长因子23与继发性甲状旁腺功能亢进关系研究进展

随着肾功能不断下降,慢性肾脏病(Chronic kidney disease,CKD)患者体内的钙磷平衡无法维持正常,甲状旁腺功能亢进随之产生,这就是继发性甲状旁腺功能亢进(Secondary hyperparathyroidism,SHPT),它是慢性肾衰竭(Chronic renal failure,CRF)的常见并发症之一.当肾小球滤过率(Glomerular filtration rate,GFR)＜ 60ml/min时,血中甲状旁腺激素(Parathyroid hormone,PTH)增高;当GFR ＜50ml/min时,PTH可明显增高;其升高程度与肾衰竭程度密切相关.活性维生素D分泌不足及磷潴留是SHPT的重要原因.     

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的疗效观察

目的观察帕立骨化醇对维持性血液透析患者继发性甲状旁腺功能亢进症的治疗效果。方法选择2018年7月至2019年7月对非选择性维生素D受体激动剂(VDRA)疗效不佳或不能耐受拟钙剂或不愿手术治疗的继发性甲状旁腺功能亢进(SHPT)的维持性血液透析患者56例,根据血液全段甲状旁腺素(iPTH)水平将所有患者分为三个组别:A组(300 pg/mL≤iPTH<600 pg/mL)、B组(600 pg/mL≤iPTH<800 pg/mL)、C组(iPTH≥800 pg/mL)。根据体重给予不同剂量的静脉帕立骨化醇注射液,分别检测患者治疗前、初始使用1个月以及达到帕立骨化醇维持剂量时,iPTH、血钙、血磷、钙磷乘积的变化情况。结果患者骨痛、瘙痒、疲乏等症状明显改善。所有患者初始治疗1个月,iPTH达标率为51.8%(29/56),达到帕立骨化醇注射液维持治疗剂量百分比为57.1%(32/56)。患者初始治疗1个月与治疗前相比,iPTH水平显著下降[(718.76±457.56)pg/mL vs.(956.68±375.61)pg/mL,P<0.001],血钙、血磷以及钙磷乘积无明显改变[(2.28±0.23)mmol/L vs.(2.23±0.27)mmol/L,(2.15±0.49)mmol/L vs.(2.29±0.48)mmol/L,(58.49±17.71)mg^2/dl2 vs.(62.90±13.93)mg^2/dl2,P>0.05]。进入维持治疗阶段的患者,维持治疗与初始治疗相比,iPTH水平仍有下降趋势,但差异无统计学意义[(424.82±221.23)pg/mL vs.(517.55±325.77)pg/mL,P>0.05],血钙、血磷以及钙磷乘积比较差异无统计学意义[(2.33±0.20)mmol/L vs.(2.31±0.24)mmol/L,(2.13±0.44)mmol/L vs.(2.00±0.42)mmol/L,(61.24±12.25)mg^2/dl2 vs.(55.76±15.66)mg^2/dl2,P>0.05]。结论帕立骨化醇对非选择性VDRA疗效不佳或不能耐受拟钙剂或不愿手术治疗的维持性血液透析患者SHPT有较好的疗效,明显缓解患者骨痛、瘙痒、疲乏等症状,显著降低iPTH水平,且不增加高钙血症的发生风险。     

维持性血液透析患者继发性甲旁亢的手术治疗疗效观察

目的 回顾性总结维持性血液透析患者继发性甲状旁腺功能亢进症(secondary hyperparathyroidism,SHPT)行甲状旁腺切除术(parathyroidectomy,PTX)的临床疗效.方法 收集2009年10月～2013年11月的25例血液透析患者(平均透析龄58±18.7个月;平均年龄45.6±8.3岁).监测术后并发症及复发情况.对比分析患者术前及术后1个月、3个月、6个月的临床症状、全段甲状旁腺激素(intact parathyroid hormone,iPTH)、血清钙、血清磷及碱性磷酸酶等变化.结果 25例患者中,甲状旁腺全切术共24例(占96％),甲状旁腺全切加前臂自体移植术1例(占4％).术后围手术期无死亡发生.术后绝大部分患者的骨痛及皮肤瘙痒症状在数天内缓解,但随着随访时间的延长,术前颈部彩色超声示小于4枚甲状旁腺结节性增大的5例患者骨痛症状均有复发(20％),但程度较术前明显减轻.2例患者出现一过性声音嘶哑(发生率8％).术后全部患者均出现低钙血症(发生率100％),经积极补钙治疗后均可有效控制.25例患者术前均表现为明显增高的iPTH、血清钙、血清磷和ALP.术后iPTH(P＜0.01)、血清钙(P＜0.01)、血清磷(P＜0.01)和ALP(P＜0.01)水平均较术前显著降低.随访6个月,5例复发(20％),且均为术前检查小于4枚甲状旁腺结节性增大的患者.结论 PTX治疗维持性血液透析患者继发性甲旁亢是一种相对安全和有效的方法,但其长期疗效仍有待于进一步观察.     

慢性肾衰竭患者继发甲状旁腺功能亢进外科治疗进展

随着透析技术的进步,慢性肾衰竭患者的生存时间逐渐延长,但影响患者生活质量甚至严重威胁患者生命的许多并发症也随之出现.继发性甲状旁腺功能亢进(SHPT)是血液透析患者的常见并发症之一,并且有一定的发病率和病死率,特征性表现主要有:低钙、高磷和高甲状旁腺激素.大多数患者可以通过药物治疗而痊愈,然而,药物治疗并不是都能很好地调节甲状旁腺功能的紊乱,部分患者需要外科干预.本文对慢性肾衰竭血透患者SHPT外科治疗的现状做一综述.

Abstract：

With the development of the dialysis technology,the survival time of patients with chronic renal failure is prolonged,while more complications which affect the quality of life or even threat the life of patients are followed.Secondary hyperparathyroidism(SHPT)with a certain incidence and mortality is one of the common complications,and its main characteristic performances ale hyperphosphatemia,hypocalcemia and high level of parathyroid hormone.Most patients Can be cured by the treatment of medicine while surgical treatment is still required by some cases in which the disorder of the parathyroid function can not be well regulated through medicine treatment.The purpose of this paper is to make a review of the recent studies of surgical treatment in patients with SHPT.     

继发性甲状旁腺功能亢进症的外科治疗

继发性甲状旁腺功能亢进症(SHPT)是由于各种原因引起机体低血钙或高血磷,长期刺激甲状旁腺分泌过量的甲状旁腺素而导致的一种临床综合征。当药物及一般治疗效果不佳时就进展成为难治性SHPT,此时通过手术或局部介入性治疗可获得良好疗效。笔者从手术治疗和局部介入治疗方面探讨外科治疗SHPT疗效,并讨论分析这些治疗方法的前景。     

Chronic acid-base perturbations in hemodialysis patients treated with sevelamer hydrochloride: a two-year follow-up study

Abstract:  Sevelamer hydrochloride (HCl) contains multiple amines that may cause a significant dietary acid load. To evaluate the impact of sevelamer on arterial blood gases, we followed two groups of stable hemodialysis patients for 24 months. The Sevelamer Group ( n  = 7) did not achieve the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) goals for phosporus and Ca × P product and was switched from a calcium-based to sevelamer-based regimen. The Calcium Group ( n  = 7) achieved those goals and remained on calcium salts. Following sevelamer administration, a deterioration of chronic metabolic acidosis was revealed, which lasted throughout the study. Sevelamer therapy was associated with reduced cholesterol levels, improved serum phosphate, and Ca × P product, which facilitated the management of secondary hyperparathyroidism. No significant changes in acid–base status or other parameter tested were found in the Control Group. In conclusion, sevelamer intake caused small but persistent acid–base disturbances, which did not neutralize sevelamer's beneficial effects on mineral and lipid metabolism.     

血液透析患者中心静脉狭窄的临床特点、血管腔内治疗的效果观察

目的 探讨血液透析患者中心静脉狭窄(central vein stenosis,CVS)的临床特点以及对其实施血管腔内治疗的临床疗效.方法 选取2012年1月至2014年1月于本院行血液透析治疗且合并有中心静脉狭窄的36例患者为研究对象,采用静脉造影技术,分析其临床特点,并对其实施血管腔内治疗,观察其治疗效果.结果 本组患者包括27例中心静脉狭窄与9例中心静脉闭塞.其中,狭窄位于右侧锁骨下静脉与头臂静脉交汇处13例(36.11%),左侧头臂静脉近心端8例(22.22%),右侧头臂静脉近心端4例(11.11%),右侧腋静脉伴锁骨下静脉2例(5.56%);闭塞位于左侧头臂静脉4例(11.11%),右侧锁骨下近端5例(13.89%).36例患者中有24例行经皮血管支架植入术(pecutaneous transtuminl stenting,PTS)或经皮血管球囊扩张成形术(pecutaneous transtuminl angioplasty,PTA)联合治疗,其余12例行PTA治疗,治疗1周后患者上肢、腋部与胸壁浅表静脉曲张缓解或消失;随访期间有6例患者复发,且均为行PTA治疗的患者.结论 掌握中心静脉狭窄的临床特点,有助于患者的早期诊治,对预后具有重要意义;血液透析合并中心静脉狭窄患者行单纯PTA或PTS与PTA联合治疗,均可取得较好的治疗效果,但PTA治疗后复发的可能性较高.     

Early initiation of cinacalcet for the treatment of secondary hyperparathyroidism in hemodialysis patients: a three-year clinical experience

Despite the availability of standard therapy (vitamin D sterols and phosphate binders) for the treatment of secondary hyperparathyroidism (SHPT) in hemodialyzed (HD) patients, a significant percentage of patients still fail to achieve targets recommended by the Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation for parathyroid hormone (PTH), calcium, and phosphorus. The calcimimetic cinacalcet (CN) has been shown to be an effective treatment for SHPT, significantly reducing serum PTH while simultaneously lowering calcium, phosphorus, and calcium-phosphorus product levels, thus increasing the proportion of patients achieving the K/DOQI targets for bone mineral parameters. The aim of this study was to evaluate if early treatment with CN had beneficial effects in HD patients with mild-to-moderate SHPT in whom conventional treatments had failed to achieve NKF-K/DOQI targets for PTH, serum-corrected calcium, and phosphorus while minimizing the risk of paradoxical hypercalcemia and/or hyperphosphatemia. Clinical practice data were collected monthly, starting from 6 months prior to, and up to 36 months after, the start of CN therapy. CN was started at a dose of 30 mg daily or every other day, and titrated thereafter to achieve intact PTH (iPTH) <300 pg/mL. The dose of concomitant vitamin D and phosphate binders were also adjusted in order to achieve K/DOQI targets. Data from 32 patients were collected, 28 of whom had been treated with CN for at least 36 months at the time of data analysis. At baseline, patients had serum iPTH >300 pg/mL (570 ± 295 pg/mL) and/or serum-corrected calcium >9.5 mg/dL. CN induced significant decreases in iPTH, calcium, and calcium-phosphorus product with respect to baseline levels. The percentage of patients within K/DOQI target levels at baseline, 12, 24, and 36 months was 0, 81.2, 83.3, and 86.2% for iPTH; 34.4, 65.6, 86.6, and 89.6% for serum-corrected calcium; 40.6, 56.2, 69.6, and 72.4% for phosphorus; and 37.5, 62.5, 80, and 82.7% for calcium-phosphorus product. The mean dose of CN at the end of the observation period was 38 mg/day. The mean dose of concomitant medication (calcitriol, Al-containing phosphate binders, and sevelamer) decreased from baseline to 36 months. Early treatment with CN in HD patients with SHPT increases the proportion of patients achieving and maintaining K/DOQI targets with a low dose of CN (38 mg/day). These results suggest that the metabolic control obtained with low-dose CN administered early in the course of SHPT can be maintained or increased over time.     

继发性甲状旁腺功能亢进疾病相关分子的筛选与验证

背景与目的：继发性甲状旁腺功能亢进（SHPT）是慢性肾脏疾病（CKD）最棘手的并发症之一,伴随着一系列的钙磷代谢紊乱、骨软化症与小肠吸收不良等症状,严重影响了患者的生存质量。目前临床上治疗效果不佳,尚未发现理想的靶点分子。因此,本研究旨在寻找SHPT的疾病相关分子,从而为其治疗提供新的靶点。方法：收集2017—2020年中南大学湘雅医院病理科5例新鲜正常甲状旁腺组织,15例SHPT患者甲状旁腺组织,其中2例正常甲状旁腺组织及5例SHPT患者甲状旁腺组织用于RNA转录组测序,获取差异表达基因,并通过功能富集分析、构建PPI网络和拓扑算法识别出核心基因;分别用qRT-PCR法与Western blot法验证核心基因在其余正常甲状旁腺组织与SHPT甲状旁腺组织中的表达。采用免疫组化法检测核心基因在36例SHPT甲状旁腺组织石蜡标本与16例甲状腺手术误切的正常甲状旁腺石蜡标本中的表达。结果：RNA测序发现1 323个差异基因;构建PPI网络和拓扑算法,最终筛选出10个关键基因;其中,二肽基肽酶4 (DPP4)因与糖尿病密切相关,而被用于进一步的验证。qRT-PCR结果显示,SHPT患者甲状旁腺...