Effects of different dialysis modalities on long-term prognosis after parathyroidectomy in patients with secondary hyperparathyroidism

Liu Xiaoyi, Zhang Zhe, Xie Chao, Hou Aizhen, Ye Peiyi, Kong Yaozhong

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Chinese Journal of Nephrology ›› 2022, Vol. 38 ›› Issue (5) : 406-412. DOI: 10.3760/cma.j.cn441217-20210907-00058
Clinical Study

Effects of different dialysis modalities on long-term prognosis after parathyroidectomy in patients with secondary hyperparathyroidism

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Abstract

Objective To compare the survival rate of secondary hyperparathyroidism (SHPT) patients with different dialysis modalities after parathyroidectomy (PTX), and analyze the influencing factors of survival prognosis. Methods Clinical data of dialysis patients diagnosed with SHPT and treated with PTX in the First Peoples Hospital of Foshan from April 2014 to May 2019 were retrospectively collected and analyzed. The patients were divided into hemodialysis (HD) group and peritoneal dialysis (PD) group according to preoperative dialysis modalities, and the differences in baseline clinical data and cardiac ultrasound results were compared between the two groups. Kaplan-Meier survival analysis was used to compare the difference in cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the influencing factors of all-cause death. Receiver operating characteristic curve (ROC curve) was used to predict the risk of all-cause death. Results A total of 99 patients were enrolled in this study, and 94 patients completed follow-up, including 23 patients who died. Compared with PD group (n=45), HD group (n=54) had higher dialysis age, blood pressure, intact parathyroid hormone, alkaline phosphatase, total heart valve calcification rate, mitral valve calcification proportion, interventricular septal thickness (IVST) and left ventricular mass index (all P<0.05). The median follow-up time was 46.00(32.75, 60.25) months. Kaplan-Meier survival analysis showed that there was no significant difference in cumulative survival rate between HD group and PD group (Log-rank test χ2=0.414, P=0.520). Multivariate Cox regression analysis showed that increasing age (HR=1.066, 95%CI 1.017-1.118, P=0.008), systolic blood pressure>140 mmHg (HR=2.601, 95%CI 1.002-6.752, P=0.049) and increasing IVST (HR=1.269, 95%CI 1.036-1.554, P=0.021) were independent influencing factors for all-cause death in dialysis patients after PTX. ROC curve analysis results showed that the cut-off values of age, dialysis age and IVST for predicting all-cause death after PTX were 51.5 years old (AUC=0.673, 95%CI 0.545-0.802, P=0.013) and 75.0 months (AUC=0.654, 95%CI 0.528-0.780, P=0.027) and 13.5 mm (AUC=0.680, 95%CI 0.557-0.803, P=0.010) respectively. The area under the ROC curve for age, dialysis age, IVST, left ventricular hypertrophy in combination with systolic blood pressure>140 mmHg in the prediction of all-cause death after PTX was 0.776(95%CI 0.677-0.875, P<0.001). Conclusions There is no significant difference in cumulative survival rate between HD and PD patients with SHPT after PTX. Increasing age, systolic blood pressure>140 mmHg and increasing IVST are independent risk factors for all-cause death in dialysis patients with SHPT after PTX.

Key words

Hyperparathyroidism, secondary / Parathyroidectomy / Renal dialysis / Peritoneal dialysis / Prognosis

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Liu Xiaoyi. , Zhang Zhe. , Xie Chao. , Hou Aizhen. , Ye Peiyi. , Kong Yaozhong. Effects of different dialysis modalities on long-term prognosis after parathyroidectomy in patients with secondary hyperparathyroidism[J]. Chinese Journal of Nephrology, 2022, 38(5): 406-412. DOI: 10.3760/cma.j.cn441217-20210907-00058.
继发性甲状旁腺功能亢进症(secondary hyperparathyroidism,SHPT)是慢性肾脏病患者的常见并发症。当药物治疗SHPT无效时,甲状旁腺切除术(parathyroidectomy,PTX)为难治性SHPT的有效手段。成功的PTX不仅可改善SHPT患者的骨痛、皮肤瘙痒等临床症状,提高患者生活质量,还大大降低透析患者的心血管事件及全因死亡的发生风险[1-2]。近年来,有研究者发现,相比血液透析(hemodialysis,HD),腹膜透析(peritoneal dialysis,PD)合并SHPT患者PTX术后的低钙血症的临床病程和住院时间显著较短[3]。目前有关不同透析方式对SHPT患者PTX术后生存预后的影响尚不明确。本研究旨在探讨不同透析方式的SHPT患者PTX术后生存预后的差异,并分析患者生存预后的影响因素。

对象与方法

一、 研究对象

纳入2014年4月至2019年5月在佛山市第一人民医院确诊SHPT并首次接受甲状旁腺全切+自体移植术的患者为研究对象。纳入标准:(1)年龄≥18岁;(2)接受维持性透析治疗时间>3个月;(3)确诊SHPT并符合PTX手术指证;(4)首次接受PTX治疗。排除标准:未行透析治疗;接受过PTX治疗者。本研究获佛山市第一人民医院伦理委员会审核批准(审批文号:L[2021]第13号),所有研究对象均签署知情同意书。

二、 研究方法

1. 研究设计: 本研究为单中心、回顾性研究。根据术前透析治疗方式分为HD组和PD组,随访时间截至2021年5月31日,记录患者随访期间全因死亡事件。
2. 临床资料收集: (1)一般资料:包括性别、年龄、体重指数(BMI)、血压、透析方式、透析龄、原发病、术前活性维生素D及磷结合剂使用情况等;(2)实验室检查:术前血白蛋白、全段甲状旁腺素(iPTH)、血钙、血磷、血碱性磷酸酶(ALP)及术后血钙、血磷及iPTH等;(3)术前心脏超声检查:包括左心室射血分数(LVEF)、舒张末期室间隔厚度(IVST)、左心室后壁厚度(LVPWT)、舒张末期左心室内径(LVED)、心脏瓣膜钙化情况等。
3. 相关定义: (1)术后严重低钙血症:术后72 h内血清总钙≤1.85 mmol/L[4]。(2)残余肾功能评估:HD患者透析前24 h尿量≥100 ml视为有残余肾功能;24 h尿量<100 ml视为无残余肾功能[5]。(3)瓣膜钙化:任一心脏瓣膜(包括二尖瓣、三尖瓣、主动脉瓣和肺主动脉瓣)出现1个或多个>1 mm的环面亮回声。总心脏瓣膜钙化率(%)=钙化的心脏瓣膜总数/总心脏瓣膜数。(4)左心室肥厚:根据Devereu公式[6]计算左心室质量指数(LVMI,g/m2),LVMI=左心室质量(LVM)/体表面积(BSA),其中LVM(g)=0.8×1.04×{[LVED(cm)+IVST(cm)+LVPWT(cm)]3-[LVED(cm)]3}+0.6;BSA(m2)=0.0061×身高(cm)+0.0124×体重(kg)-0.0099。左心室肥厚定义为男性LVMI>125 g/m2,女性LVMI>110 g/m2

三、 统计学方法

采用SPSS 25.0软件进行数据的统计学处理。呈正态分布的计量资料用x¯±s形式表示,两组间比较采用独立样本t检验;非正态分布的计量资料用MP25P75)形式表示,两组间比较采用Mann-Whitney U秩和检验。计数资料用例数及百分比表示,两组间比较采用卡方检验。采用Kaplan-Meier法绘制生存曲线,Log-rank检验比较两组患者生存率的差异。采用多因素Cox回归模型法分析患者全因死亡的影响因素。采用受试者工作特征曲线(ROC曲线)预测患者全因死亡的风险。P<0.05视为差异有统计学意义。

结果

1. 基线资料: 99例接受过PTX的SHPT患者被纳入本研究,年龄(50.03±11.48)岁,其中男性47例(47.47%),女性52例(52.53%)。原发病包括慢性肾小球肾炎73例(73.74%)、梗阻性肾病13例(13.13%)、糖尿病肾病5例(5.05%)及其他8例(8.08%)。与PD组比较,HD组患者收缩压、舒张压、透析龄、血红蛋白、血清白蛋白、ALP、iPTH、铁蛋白水平及直径≥2 cm的甲状旁腺增生结节数目较高,而BMI及有残余肾功能比例较低,两组间比较差异均有统计学意义(均P<0.05)。两组间其他项目的差异均无统计学意义(均P>0.05)。见表1
表1 HD组与PD组患者基线临床资料的比较
项目 总体(n=99) HD组(n=54) PD组(n=45) 统计值(t/χ2/Z) P
年龄(岁) 50.03±11.48 49.02±12.67 51.24±9.85 -1.157 0.247
男/女(例) 47/52 27/27 20/25 0.304 0.582
体重指数(kg/m2) 21.45(19.74,23.71) 20.46(18.68,23.30) 22.04(20.37,24.22) -2.410 0.016
收缩压(mmHg) 136.92±26.38 141.50(124.00,154.50) 132.00(112.50,141.50) -2.407 0.016
舒张压(mmHg) 84.65±14.31 87.43±14.38 81.31±13.66 2.155 0.034
透析龄(月) 72.00(60.00,96.00) 84.00(69.25,108.00) 60.00(51.00,85.00) -3.187 0.001
原发病[例(%)] 5.391 0.139
慢性肾小球肾炎 73(73.74) 36(66.67) 37(82.22)
梗阻性肾病 13(13.13) 7(12.96) 6(13.33)
糖尿病肾病 5(5.05) 4(7.41) 1(2.22)
其他 8(8.08) 7(12.96) 1(2.22)
血红蛋白(g/L) 109.66±20.06 113.74±19.67 104.76±19.64 2.265 0.026
血清白蛋白(g/L) 38.28±4.39 39.92±3.91 36.33±4.16 4.421 <0.001
ALP(U/L) 330.00(172.00,530.00) 384.00(211.25,704.00) 198.00(111.50,404.00) 3.377 0.001
血钙(mmol/L) 2.45±0.22 2.44±0.23 2.46±0.21 -0.240 0.811
血磷(mmol/L) 2.27(1.90,2.63) 2.23(1.85,2.62) 2.30(1.93,2.67) -0.727 0.467
钙磷乘积 5.70±1.50 5.41(4.54,6.52) 5.76(4.86,6.38) -0.791 0.429
血清iPTH(ng/L) 2 056.0(1 426.0,2 500.0) 2 174.5(1 767.5,2 500.0) 1 587.0(1 163.0,2 406.5) -2.943 0.003
eGFR 4.33(3.12,5.50) 4.27(3.31,5.43) 4.50(2.91,5.54) -0.337 0.736
有残余肾功能[例(%)] 17(17.17) 3(5.56) 14(31.11) 11.271 0.001
血肌酐(μmol/L) 981.52±237.31 964.85±224.06 1 001.51±253.41 -0.764 0.447
血尿酸(μmol/L) 434.62±134.57 424.50(335.75,550.50) 432.00(392.00,493.00) -0.355 0.723
血清铁蛋白(μg/L) 199.20(89.80,483.10) 413.90(86.35,831.78) 145.50(91.30,229.75) -3.046 0.002
甲状旁腺增生结节数目[枚(%)] 11.685 0.001
直径<2 cm 235(83.63)(n=281) 125(77.16)(n=162) 110(92.44)(n=119)
直径≥2 cm 46(16.37)(n=281) 37(22.84)(n=162) 9(7.56)(n=119)
服用活性维生素D[例(%)] 58(58.59) 32(59.26) 26(57.78) 0.022 0.882
服用磷结合剂[例(%)] 72(72.73) 42(77.78) 30(66.67) 1.528 0.216
术后7 d血钙(mmol/L) 2.16±0.28 2.15±0.28 2.16±0.28 -0.177 0.860
术后7 d血磷(mmol/L) 0.89(0.68,1.20) 0.84(0.68,1.20) 0.91(0.67,1.20) -0.295 0.768
术后严重低钙血症[例(%)] 30(30.30) 20(37.04) 10(22.22) 2.551 0.110
注:HD:血液透析;PD:腹膜透析;ALP:碱性磷酸酶;iPTH:全段甲状旁腺素;eGFR:估算肾小球滤过率,单位为ml∙min-1∙(1.73 m2)-1;术后严重低钙血症:术后72 h内血清总钙≤1.85 mmol/L;1 mmHg=0.133 kPa;呈正态分布的计量资料用x¯±s形式表示,非正态分布的计量资料用MP25P75)形式表示,计数资料用例数及百分比表示
2.心脏彩超检查:99例患者中有63例(63.64%)患者存在心脏瓣膜钙化,其中33例(33.33%)患者同时存在主动脉瓣和二尖瓣2个部位的心脏瓣膜钙化。两组患者心脏瓣膜钙化均以主动脉瓣瓣膜钙化最为常见(55.56%比48.89%),其次为二尖瓣瓣膜钙化(53.70%比26.67%),没有观察到三尖瓣及肺动脉瓣瓣膜钙化,两组患者心脏瓣膜钙化发生率的差异无统计学意义( χ2=1.224,P=0.269)。HD组患者IVST、LVPWT、LVMI、左心室肥厚占比、总心脏瓣膜钙化率和二尖瓣瓣膜钙化比例高于PD组(均P<0.05)。见表2
表2 HD组与PD组患者PTX术前心脏彩超检查结果的比较
项目 总体(n=99) HD组(n=54) PD组(n=45) 统计值(t/χ2/Z) P
LVEF(%) 61.94±7.16 62.41±7.18 61.38±7.39 0.701 0.485
LVED(mm) 45.00(41.00,49.00) 45.00(41.75,49.00) 43.00(39.00,48.00) -1.214 0.225
LVDs(mm) 30.00(26.00,33.00) 30.00(26.50,33.25) 29.00(25.50,33.00) -0.807 0.420
IVST(mm) 13.00(12.00,15.00) 14.00(12.00,16.00) 13.00(12.00,14.00) -2.289 0.022
IVSs(mm) 18.00(16.00,19.00) 18.00(16.00,19.00) 17.00(16.00,19.00) -1.409 0.159
LVPWT(mm) 12.00(11.00,13.00) 12.00(11.00,14.00) 12.00(11.00,13.00) -2.164 0.030
LVMI(g/m2) 132.40(98.40,159.62) 147.59(114.42,170.89) 113.78(94.85,136.55) -3.008 0.003
左心室肥厚[例(%)] 62(62.63) 41(75.93) 21(46.67) 8.978 0.003
心脏瓣膜钙化[例(%)] 63(63.64) 37(68.52) 26(57.78) 1.224 0.269
主动脉瓣钙化[例(%)] 52(52.53) 30(55.56) 22(48.89) 0.437 0.508
二尖瓣钙化[例(%)] 41(41.41) 29(53.70) 12(26.67) 7.395 0.007
总心脏瓣膜钙化率[瓣(%)] 93(23.48)(n=396) 59(27.31)(n=216) 34(18.89)(n=180) 3.879 0.049
注:HD:血液透析;PD:腹膜透析;PTX:甲状旁腺切除术;LVEF:左心室射血分数;LVED:舒张末期左心室内径;LVDs:收缩末期左心室内径;IVST:舒张末期室间隔厚度;IVSs:收缩末期室间隔厚度;LVPWT:左心室后壁厚度;LVMI:左心室质量指数;呈正态分布的计量资料用x¯±s形式表示,非正态分布的计量资料用MP25P75)形式表示,计数资料用例数及百分比表示
3. 临床结局及生存分析: 随访日期截至2021年5月31日,共94例患者完成随访,其中死亡23例(24.47%),主要死因包括心脏疾病6例、脑出血5例、感染2例、原因不明10例。23例死亡患者中HD组13例(56.52%),PD组10例(43.48%)。中位随访时间为46.00(32.75,60.25)个月,Kaplan-Meier生存分析结果显示,HD组与PD组患者累积生存率的差异无统计学意义(Log-rank检验 χ2=0.414,P=0.520)。见图1
图1 血液透析与腹膜透析患者累积生存率的比较(Kaplan-Meier生存分析)

Full size|PPT slide

4. 全因死亡的影响因素: 单因素Cox比例风险回归模型分析结果显示,年龄增加、收缩压>140 mmHg和IVST增加是PTX术后患者全因死亡的影响因素(均P<0.05)。校正基线资料包括性别、透析方式、透析龄、血iPTH、残余肾功能、左心室肥厚、心脏瓣膜钙化、术后7 d钙磷水平及术后严重低钙血症等因素后,多因素Cox比例风险回归模型分析结果显示年龄增加(HR=1.066,95%CI 1.017~1.118,P=0.008)、收缩压>140 mmHg(HR=2.601,95%CI 1.002~6.752,P=0.049)及IVST增厚(HR=1.269,95%CI 1.036~1.554,P=0.021)仍是PTX术后患者全因死亡的独立影响因素,见表3
表3 甲状旁腺切除术患者全因死亡的影响因素分析(Cox回归模型,n=94)
影响因素 单因素分析 多因素分析
HR(95%CI) P HR(95%CI) P
男性(是/否) 1.081(0.476~2.451) 0.853
年龄(岁) 1.051(1.013~1.090) 0.008 1.066(1.017~1.118) 0.008
血液透析(是/否) 1.311(0.573~2.997) 0.522
透析龄(月) 1.011(0.998~1.023) 0.097
收缩压>140 mmHg(是/否) 2.307(1.009~5.272) 0.047 2.601(1.002~6.752) 0.049
iPTH(ng/L) 1.000(1.000~1.000) 0.962
残余肾功能(有/无) 0.382(0.089~1.637) 0.195
IVST(mm) 1.163(1.009~1.340) 0.038 1.269(1.036~1.554) 0.021
左心室肥厚(有/无) 2.579(0.957~6.953) 0.061
心脏瓣膜钙化(有/无) 1.437(0.590~3.503) 0.425
术后7 d血钙(mmol/L) 0.349(0.080~1.518) 0.161
术后7 d血磷(mmol/L) 0.919(0.364~2.320) 0.858
术后严重低钙血症(有/无) 0.953(0.392~2.317) 0.915
注:iPTH:全段甲状旁腺素;IVST:舒张末期室间隔厚度;1 mmHg=0.133 kPa
5. 全因死亡的风险预测: ROC曲线分析结果显示,年龄、透析龄和IVST预测患者PTX术后全因死亡的截断值分别为51.5岁(AUC=0.673,95%CI 0.545~0.802,P=0.013)、75.0个月(AUC=0.654,95%CI 0.528~0.780,P=0.027)和13.5 mm(AUC=0.680,95%CI 0.557~0.803,P=0.010)。年龄+透析龄+IVST+左心室肥厚+收缩压>140 mmHg联合预测透析患者PTX术后全因死亡的AUC为0.776(95%CI 0.677~0.875,P<0.001),敏感度为91.30%,特异度为63.38%。见表4
表4 透析患者甲状旁腺切除术后全因死亡的风险预测分析(ROC曲线)
因素 截断值 AUC 敏感度(%) 特异度(%) 95%CI P
年龄 51.5岁 0.673 65.22 63.38 0.545~0.802 0.013
透析方式(HD/PD) 0.485 43.48 53.52 0.349~0.621 0.829
透析龄 75.0个月 0.654 73.91 66.20 0.528~0.780 0.027
IVST 13.5 mm 0.680 69.57 61.97 0.557~0.803 0.010
左心室肥厚 0.617 78.26 45.07 0.490~0.744 0.094
收缩压>140 mmHg 0.600 56.52 63.38 0.465~0.734 0.153
联合预测模型1 0.764 95.65 50.70 0.666~0.862 <0.001
联合预测模型2 0.776 91.30 63.38 0.677~0.875 <0.001
注:AUC:曲线下面积;HD:血液透析;PD:腹膜透析;IVST:舒张末期室间隔厚度;联合预测模型1:年龄+透析龄+IVST+左心室肥厚;联合预测模型2:年龄+透析龄+IVST+左心室肥厚+收缩压>140 mmHg;1 mmHg=0.133 kPa

讨论

PTX治疗SHPT可显著改善患者生活质量,提高患者的生存率[1,7],但目前PTX术后患者的死亡风险仍较高。尿毒症合并SHPT患者PTX术后1、2、3年的全因死亡率分别为6.1%、16.3%、30.4%[8]。我们对本院接受PTX手术治疗的透析患者进行随访并记录全因死亡事件,中位随访时间为46.00(32.75,60.25)个月,研究结果显示,SHPT患者PTX术后1、2、3、4和5年的全因死亡率分别为6.4%、10.8%、15.8%、21.5%和30.3%。既往有研究表明PD患者心血管钙化的发生率低于HD患者[9],且具有较好的生存优势[10]。但也有学者认为不同透析方式对终末期肾病患者生存率的影响无显著差异[11-12]。目前有关不同透析方式对SHPT患者PTX术后预后影响的研究甚少。
本研究结果显示,接近2/3的SHPT患者存在心脏瓣膜钙化及左心室肥厚,HD组和PD组患者均以主动脉瓣瓣膜钙化为主,其次为二尖瓣瓣膜钙化,两组间心脏瓣膜钙化比例的差异无统计学意义。HD组患者总的心脏瓣膜钙化率、二尖瓣瓣膜钙化比例、左心室质量指数及左心室肥厚比例显著高于PD组,可能与本研究中HD组患者的透析龄、收缩压、舒张压、ALP、血清iPTH水平均高于PD组有关。有研究表明,透析龄是透析患者心脏瓣膜钙化的独立影响因素,透析龄每增加1个月,心脏瓣膜钙化的风险增加26.1%[9]。有文献报道,血清ALP水平与透析患者心脏瓣膜钙化密切相关,透析患者血清ALP≥232 U/L是预测心脏瓣膜钙化的重要指标[13],血清iPTH水平持续升高可促进钙磷在心肌沉积,导致心肌和心脏瓣膜钙化,并且可激活成纤维细胞,促进心肌间质纤维化,增加心脏非血管间质体积,诱导心肌肥厚[14]
本研究结果显示,PD组患者的累积生存率稍高于HD组,但两组间的差异无统计学意义。这可能与两组患者PTX术后矿物质和骨代谢相关指标均得到明显改善有关。有文献报道,HD与PD患者PTX术后血iPTH和ALP水平均大幅下降,且术后两组血iPTH及ALP水平均大致相似[15]。已有的研究表明,终末期肾病患者高iPTH及ALP水平与全因死亡率升高密切相关,成功的PTX可降低严重SHPT患者心血管事件死亡及全因死亡的风险[16]。PTX术后iPTH和ALP水平下降,不但可以延缓机体心血管钙化、左心室肥厚,甚至可以一定程度逆转上述病生理改变[17-18]。有研究证实,PTX术后半年甚至1年冠状动脉血管钙化积分、LVMI、IVST、LVPWT、LVED等指标均较术前下降[19-20],有利于减少终末期肾病患者心血管事件发生,大大提高其远期生存率及生存质量。但本研究为单中心、回顾性研究,样本量较小,还需增加病例数以进一步证实研究结论。
近年来,接受PTX治疗的SHPT患者逐渐增多,但患者预后的影响因素分析的文献较少。有研究者发现,接受PTX治疗的SHPT患者的预后与术后第1周血iPTH水平相关,术后第1周血iPTH>600 ng/L是患者全因死亡风险增加的危险因素[21]。本研究Cox回归分析结果显示,年龄增加、收缩压>140 mmHg及IVST增厚是PTX术后患者全因死亡的独立危险因素。ROC曲线结果显示,年龄、透析龄、IVST、左心室肥厚及收缩压>140 mmHg联合预测患者PTX术后全因死亡风险的敏感度为91.30%,特异度为63.38%。年龄和透析龄已被公认为透析患者发生心血管疾病的传统影响因素,而合并高血压则进一步加重患者心血管钙化、心室肥厚,增加心血管事件发生的风险。因此,对于接受PTX治疗的SHPT患者,除了需管控术后血iPTH水平,术前监测和管理血压对患者预后具有重要意义。
综上所述,HD与PD患者PTX术后生存率相似,心脑血管疾病仍是PTX患者的主要死因,年龄增加、收缩压>140 mmHg及IVST增厚是PTX术后患者全因死亡的独立危险因素。

References

[1]
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Parathyroidectomy (PTx) drastically improves biochemical parameters and clinical symptoms related to severe secondary hyperparathyroidism (SHPT) but the effect of PTx on survival has not been adequately investigated. Here we analyzed data on 114,064 maintenance hemodialysis patients from a nationwide registry of the Japanese Society for Dialysis Therapy to evaluate the associations of severity of SHPT and history of PTx with 1-year all-cause and cardiovascular mortality. We then compared the mortality rate between 4428 patients who had undergone PTx and 4428 propensity score-matched patients who had not despite severe SHPT. During a 1-year follow-up, 7926 patients of the entire study population died, of whom 3607 died from cardiovascular disease. Among patients without a history of PTx, severe SHPT was associated with an increased risk for all-cause and cardiovascular mortality. However, such an increased risk of mortality was not observed among patients with a history of PTx. In the propensity score-matched analysis, patients who had undergone PTx had a 34% and 41% lower risk for all-cause and cardiovascular mortality, respectively, compared to the matched controls. The survival benefit associated with PTx was robust in several sensitivity analyses and consistent across subgroups, except for those who had persistent postoperative SHPT. Thus, successful PTx may reduce the risk for all-cause and cardiovascular mortality in hemodialysis patients with severe, uncontrolled SHPT.
[2]
Lim C, Kalaiselvam T, Kitan N, et al. Clinical course after parathyroidectomy in adults with end-stage renal disease on maintenance dialysis[J]. Clin Kidney J, 2018, 11(2): 265-269. DOI: 10.1093/ckj/sfx086.
Parathyroidectomy (PTX) is done in cases of secondary hyperparathyroidism from chronic kidney disease to improve renal osteodystrophy. Despite this widespread practice, clinical outcomes regarding the benefits of this procedure are still lacking. Most studies in the literature have opted to report the laboratory outcome instead. Our study aimed to evaluate the postoperative clinical course for patients who had undergone total PTX without autoimplantation.All patients who underwent PTX between January 2010 and February 2014 in a tertiary referral center were included in this study and followed up for 12 months. Laboratory outcome parameters include various preoperative and postoperative serial measurements of laboratory parameters. Patients' hospitalizations and mortality records post-PTX were also retrieved and recorded. In all, 90 patients were included in this study. The mean age was 48 ± 18 years. The majority of the patients (54.4%) were male and 90% were on hemodialysis. The mean duration of dialysis was 8.0 ± 5.0 years. Indications for PTX were symptomatic bone pain (95.6%), fractures (3.3%) and calciphylaxis (1.1%). Mean preoperative values for serum calcium, phosphate, alkaline phosphatase and intact parathyroid hormone (iPTH) were 2.40 ± 0.23mmol/L, 1.92 ± 0.51 mmol/L, 689.60 ± 708.50 U/L and 311.90 ± 171.94 pmol/L, respectively. The majority (92.2%) had all four glands removed and 92.2% of the glands showed hyperplasic changes. One year after PTX, 90 patients (100%) had serum iPTH <8 pmol/L and 28 patients (31%) had unmeasurable iPTH levels. A total of 15% of patients had hospitalizations for various reasons and of these, 50% were within 90 days. The mean hospital stay was 14.4 ± 18.6 days. The mortality rate was 4.4% and of these, 25% were in first 30 days. Causes of death were mainly from sepsis (75%) and acute coronary syndrome (25%). One patient (1.1%) had a relapse.Even though PTX markedly reduces postoperative serum iPTH levels, it carries with it significant risk of morbidity and mortality.
[3]
Yang G, Ge Y, Zha X, et al. Peritoneal dialysis can alleviate the clinical course of hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism[J]. Int Urol Nephrol, 2019, 51(3): 535-542. DOI: 10.1007/s11255-019-02076-7.
It is unclear whether clinical courses of hungry bone syndrome (HBS) after parathyroidectomy (PTX) in peritoneal dialysis (PD) and hemodialysis (HD) patients are different. The present study aimed to investigate the possible differences of postoperative hypocalcemia and hyperkalemia between PD and HD patients.We performed retrospectively 29 PD patients as the PD group and 169 HD patients as the HD group undergoing successful total PTX with autotransplantation. Calcium supplement after surgery was recorded. Higher levels of serum potassium during and immediately after surgery were recorded as K. K was recorded as peak pre-dialysis serum potassium level 3 days post-surgery.There were 157 (92.90%) patients in HD group and 22 (75.86%) patients in PD group suffered from HBS after surgery, with significant difference between the groups (P = 0.004). Patients in PD group had significantly shorter intravenous calcium supplement duration (P = 0.037) and significantly smaller intravenous calcium supplement dosage (P = 0.042) and total calcium supplement dosage during hospitalization (P = 0.012) than patients in HD group. The levels of serum K (P < 0.001) and K (P < 0.001) were both significantly lower in PD group than those in HD group. Peritoneal dialysis was one of the independent influencing factors with negative correlation for calcium supplement, serum K and serum K.Compared with HD patients, the clinical course of HBS after PTX in PD patients was alleviated. Efforts should be devoted to individual perioperative management for PD patients undergoing PTX.
[4]
赵沙沙, 闻萍, 甘巍, 等. 甲状旁腺全切术患者术后严重低钙血症危险因素分析[J]. 中华肾脏病杂志, 2019, 35(7):494-498. DOI: 10.3760/cma.j.issn.1001-7097.2019.07.003.
目的 探讨甲状旁腺全切术(total parathyroidectomy without autotransplantation,TPTX)患者术后严重低钙血症的发生率,并分析其危险因素。 方法 病例来自2008年9月至2017年9月期间在南京医科大学第二附属医院接受TPTX的患者。收集患者手术前后血生化检查和术前全段甲状旁腺素(iPTH)等资料,以及手术切除甲状旁腺总质量(切除腺体质量)等。二元Logistic回归模型法分析TPTX患者术后发生严重低钙血症的危险因素。 结果 783例TPTX患者年龄(46.90±10.78)岁,平均透析龄(91.36±41.75)个月,术后发生严重低钙血症者235例,发生率为30.01%。二元Logistic回归分析结果显示,术前血iPTH(OR=7.56,95%CI:1.55~36.79,P=0.01)、血碱性磷酸酶(OR=36.71,95%CI:14.75~91.36,P<0.01)、血磷(OR=1.74,95% CI:1.11~2.71,P=0.02)水平高,切除腺体质量大(OR=1.18,95%CI:1.06~1.31,P<0.01)是患者术后发生低钙血症的危险因素;术前血钙水平高是术后低钙血症(OR=0.02,95%CI:0.01~0.07,P<0.01)的保护因素。 结论 TPTX治疗继发性甲状旁腺功能亢进症术后低钙血症发生率高。术前血iPTH、血碱性磷酸酶、血磷水平高,术中切除腺体总质量大是术后发生严重低钙血症的独立危险因素。
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Parathyroidectomy (PTx) and medical treatments are both recommended for reducing serum intact parathyroid hormone (iPTH) and curing secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), but their therapeutic effects on long-term mortality are not well-known. Thus, we aim to assess such therapeutic effect of PTx. Electronic literatures published on Pubmed, Embase, and Cochrane Central Register of Controlled Trials in any language until 27 November 2015 were systematically searched. All literatures that compared outcomes (survival rate or mortality rate) between PTx-treated and medically-treated CKD patients with sHPT were included. Finally, 13 cohort studies involving 22053 patients were included. Data were extracted from all included literatures in a standard form. The outcomes of all-cause and cardiovascular mortalities were assessed using DerSimonian and Laird's random effects model. We find PTx-treated versus medically-treated patients had a 28% reduction in all-cause mortality and a 37% reduction in cardiovascular mortality. Thus, PTx versus medical treatments might reduce the risks of all-cause and cardiovascular mortalities in CKD patients with sHPT. Further studies with prospective and large-sample clinical trials are needed to find out the real effect of PTx and to assess whether mortality rates differ among patterns of PTx.
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The objective of this study was to assess the effect of parathyroidectomy (PTX) treatment on prolonging overall survival (OS) as well as decreasing levels of intact parathyroid hormone (iPTH), calcium (Ca), and phosphorus (P) in elderly hemodialysis patients with severe secondary hyperparathyroidism (SHPT).
[9]
徐庆东, 郭焕开, 陈小荷, 等. 血液透析与腹膜透析患者心脏瓣膜钙化高危因素及对临床预后的影响[J]. 疑难病杂志, 2016, 15(11): 1139-1142. DOI: 10.3969/j.issn.1671-6450.2016.11.011.
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We sought to compare survival among incident peritoneal dialysis (PD) patients to matched hemodialysis (HD) patients who received pre-dialysis care, including permanent dialysis access placement. Patients starting PD were propensity matched to those starting HD. HD patients who used a central venous catheter during the first 90 days of dialysis were excluded. Stratified Cox proportional hazards models were used to compare patient survival using both intent-to-treat and as-treated analyses. In the intent-to-treat analysis, patients were followed from the date of first dialysis until death and censored at the earliest of the following: renal transplantation, death, renal recovery, loss to follow-up or study end. In the as-treated analysis, patients were also censored at the time of modality change. A total of 1003 matched pairs were obtained from 11,301 incident patients (10,298 HD and 1003 PD). The cumulative hazard ratio for death at one year was 2.38 (95% CI 1.68-3.40) and 2.10 (1.50-2.94) for HD relative to PD patients in the as-treated and intent-to-treat analyses, respectively. The cumulative risk of death, as estimated by the cumulative hazard ratio, favored PD for almost up to 3 years of follow-up in the as-treated analysis and nearly 2 years of follow-up in the intent-to-treat analysis with no differences thereafter. The higher adjusted rate of death observed for HD patients cannot be attributed to initial use of central venous catheters or lack of pre-dialysis care.
[11]
Wong B, Ravani P, Oliver MJ, et al. Comparison of patient survival between hemodialysis and peritoneal dialysis among patients eligible for both modalities[J]. Am J Kidney Dis, 2018, 71(3): 344-351. DOI: 10.1053/j.ajkd.2017.08.028.
Although peritoneal dialysis (PD) costs less to the health care system compared to in-center hemodialysis (HD), it is an underused therapy. Neither modality has been consistently shown to confer a clear benefit to patient survival. A key limitation of prior research is that study patients were not restricted to those eligible for both therapies.Retrospective cohort study.All adult patients developing end-stage renal disease from January 2004 to December 2013 at any of 7 regional dialysis centers in Ontario, Canada, who had received at least 1 outpatient dialysis treatment and had completed a multidisciplinary modality assessment.HD or PD.Mortality from any cause.Among all incident patients with end-stage renal disease (1,579 HD and 453 PD), PD was associated with lower risk for death among patients younger than 65 years. However, after excluding approximately one-third of all incident patients deemed to be ineligible for PD, the modalities were associated with similar survival regardless of age. This finding was also observed in analyses that were restricted to patients initiating dialysis therapy electively as outpatients. The impact of modality on survival did not vary over time.The determination of PD eligibility was based on the judgment of the multidisciplinary team at each dialysis center.HD and PD are associated with similar mortality among incident dialysis patients who are eligible for both modalities. The effect of modality on survival does not appear to change over time. Future comparisons of dialysis modality should be restricted to individuals who are deemed eligible for both modalities to reflect the outcomes of patients who have the opportunity to choose between HD and PD in clinical practice.Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
[12]
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Prior studies have shown peritoneal dialysis (PD) patients to have lower or equivalent mortality to patients who receive in-center hemodialysis (HD). Medicare's 2011 bundled dialysis prospective payment system encouraged expansion of home-based PD with unclear impacts on patient outcomes. This paper revisits the comparative risk of mortality between HD and PD among patients with incident end-stage kidney disease initiating dialysis in 2006-2013.We conducted a retrospective cohort study comparing 2-year all-cause mortality among patients with incident end-stage kidney disease initiating dialysis via HD and PD in 2006-2013, using data from the US Renal Data System and Medicare. Analysis was conducted using Cox proportional hazards models fit with inverse probability of treatment weighting that adjusted for measured patient demographic and clinical characteristics and dialysis market characteristics.Of the 449,652 patients starting dialysis between 2006 and 2013, the rate of PD use in the first 90 days increased from 9.3% of incident patients in 2006 to 14.2% in 2013. Crude 2-year mortality was 27.6% for patients dialyzing via HD and 16.7% for patients on PD. In adjusted models, there was no evidence of mortality differences between PD and HD before and after bundled payment (hazard ratio, 0.96; 95% confidence interval, 0.89-1.04; P=0.33).Overall mortality for HD and PD use was similar and mortality differences between modalities did not change before versus after the 2011 Medicare dialysis bundled payment, suggesting that increased use of home-based PD did not adversely impact patient outcomes.Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
[13]
Guo J, Zeng M, Zhang Y, et al. Serum alkaline phosphatase level predicts cardiac valve calcification in maintenance hemodialysis patients[J]. Blood Purif, 2020, 49(5): 550-559. DOI: 10.1159/000505846.
&lt;b&gt;<i>Purpose:</i>&lt;/b&gt; Cardiac valve calcification (CVC) is frequently occurred in maintenance hemodialysis (MHD) patients and is associated with cardiovascular and all-cause mortality. This study aimed to evaluate the relationships between risk factors and extent of CVC and further provide the treatment target in MHD patients. &lt;b&gt;<i>Methods:</i>&lt;/b&gt; One hundred and forty-five patients who received MHD ≥3 months were enrolled. CVC was assessed by an echocardiographic, semi-quantitative manner called global cardiac calcium scoring system (GCCS), and demographic, clinical, and laboratory parameters including mineral metabolism markers were collected. &lt;b&gt;<i>Results:</i>&lt;/b&gt; The average age of the patients was 50 ± 12 years, and 54.5% were men. The mean GCCS was 1.8 ± 2.4; 57.2% of patients had GCCS ≥1. Age, dialysis vintage, serum alkaline phosphatase (ALP), and intact parathyroid hormone levels were positively correlated with CVC, whereas serum albumin levels were negatively related to CVC, based on univariate analysis. With multivariate linear regression analysis, serum ALP was the only bone-derived biomarker that showed significant correlation with CVC. Serum ALP ≥232 U/L was a robust predictor of CVC and was associated with the likelihood of GCCS ≥1 (OR 3.92, 95% CI 1.37–11.2, <i>p</i> = 0.011). The decision tree model was used to identify ALP ≥232 U/L and age ≥60 years as important determinative variables in the prediction of CVC in MHD patients. &lt;b&gt;<i>Conclusion:</i>&lt;/b&gt; Serum ALP level is significantly associated with CVC in MHD patients. ALP is suggested to be a promising interventional target for cardiovascular calcification in MHD patients.
[14]
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[18]
侯爱珍, 肖观清, 叶佩仪, 等. 甲状旁腺切除术后维持性血液透析患者腹主动脉钙化的改变[J]. 中华肾脏病杂志, 2020, 36(3): 183-188. DOI: 10.3760/cma.j.cn441217-20190926-00037.
目的 观察维持性血液透析(maintenance hemodialysis,MHD)合并继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)患者行甲状旁腺切除术(parathyroidectomy,PTX)后腹主动脉钙化及生化指标的发展变化。 方法 回顾性分析完成2年随访的严重SHPT患者,按是否行PTX分成PTX手术组和非手术组,观察术后2年腹主动脉钙化评分(abdominal aortic calcification score,AACS)、血清全段甲状旁腺素(iPTH)、血钙、血磷等变化。PTX手术组按照术后2年腹主动脉钙化有无进展分为进展组和非进展组,对比两组的年龄、透析龄、iPTH、血钙、血磷、钙磷乘积等指标,分析腹主动脉钙化进展的相关因素。 结果 共纳入44例MHD合并SHPT患者,PTX手术组26例,非手术组18例。PTX手术组与非手术组基线资料比较,透析龄差异有统计学意义(P<0.05),而性别、年龄、高血压史等差异均无统计学意义。与术前比较,PTX手术组患者术后2年血iPTH、血钙、血磷均降低(均P<0.05),AACS前后差异无统计学意义。患者术后2年有8例(30.77%)腹主动脉钙化加速进展,8例(30.77%)腹主动脉钙化好转,10例(38.46%)腹主动脉钙化稳定。患者术后2年腹主动脉钙化非进展组iPTH值低于进展组[(20.62±6.44)ng/L比(132.72±76.83)ng/L,P<0.05],而非进展组术前AACS高于进展组[(13.11±2.71)分比(2.00±1.41)分,P<0.05]。非手术组患者2年后AACS高于基线水平[(10.44±1.65)分比(8.05±1.26)分,P<0.05],血磷及钙磷乘积显著下降(均P<0.05),iPTH、血钙等水平无明显变化(均P>0.05)。Pearson相关分析结果显示,PTX手术组术后2年AACS相对于术前的下降值与iPTH下降值(r=0.534,P=0.012)、血钙下降值(r=0.643,P=0.004)、血磷下降值(r=0.897,P<0.001)、钙磷乘积的下降值(r=0.568,P=0.021)呈正相关,与术前AACS值呈负相关(r=-0.647,P=0.014)。 结论 小样本资料显示,相比非手术治疗,PTX可长期纠正甲状旁腺素、钙、磷代谢紊乱,并有阻止腹主动脉钙化进展甚至逆转血管钙化的可能,而腹主动脉钙化逆转可能与iPTH、血Ca、血P、钙磷乘积的下降程度相关。
[19]
沈英, 张萍, 蒋华, 等. 甲状旁腺切除对尿毒症继发甲状旁腺功能亢进患者贫血和心功能的影响[J]. 中华肾脏病杂志, 2018, 34(5): 321-326. DOI: 10.3760/cma.j.issn.1001-7097.2018.05.001.
目的 探讨甲状旁腺全切(PTX)加前臂种植术对尿毒症继发性甲状旁腺功能亢进(SHPT)患者贫血及心功能的影响。 方法 回顾性分析浙江大学附属第一医院2010年10月至2015年12月接受甲状旁腺全切+前臂种植术的130例尿毒症患者的临床资料,比较手术前后贫血、超声心动图指标等变化。根据术前是否存在左心室肥厚(LVH)分为LVH组和非LVH组,比较两组患者术前及术后1年超声心动图指标变化。 结果 与术前组相比,术后3个月组、1年组患者血红蛋白、红细胞比容显著升高,红细胞生成素用量显著减少(均P<0.01)。与术前组相比,术后1年组患者干体重显著增加,心脏超声指标左室舒张末内径(LVDd)、室间隔舒张末厚度(IVSd)、左室后壁舒张末厚度(LVPWd)、室间隔收缩期厚度(IVSs)、左室收缩期内径(LVDs)、左心室心肌重量(LVM)、左心室心肌重量指数(LVMI)显著下降(均P<0.05)。LVH组患者术后1年组LVDs、LVDd、LVPWd、LVM、LVMI、IVSs均较术前组显著下降(均P<0.05);非LVH组患者术后1年组仅IVSs较术前组下降(P<0.05)。 结论 PTX加前臂移植术是难治性SHPT有效的治疗手段,能明显改善贫血及左心室结构和功能,尤其对于术前存在左心室肥厚的患者。
[20]
刘文, 于颖娟, 张林, 等. 甲状旁腺全切术对尿毒症继发甲状旁腺功能亢进症患者冠脉钙化及左心室肥厚的影响[J]. 现代医学, 2017, 45(10): 1438-1441. DOI: 10.3969/j.issn.1671-7562.2017.10.012.
[21]
Xi QP, Xie XS, Zhang L, et al. Impact of different levels of iPTH on all-cause mortality in dialysis patients with secondary hyperparathyroidism after parathyroidectomy[J]. Biomed Res Int, 2017, 2017: 6934706. DOI: 10.1155/2017/6934706.

刘晓怡:数据收集、整理、统计学分析及论文撰写;张喆、谢超:研究指导、论文修改;侯爱珍:数据收集及整理;叶佩仪、孔耀中:研究指导、论文修改及经费支持

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Construction Project of Medical Science and Technology innovation Platform of Foshan(FSOAA-KJ218-1301-0033)
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