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Volume 46 Issue 1
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Article Navigation >  Journal of Bengbu Medical College  > 2021,  46 > 1: (46-49)  

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Clinical study of pulmonary artery hypertension in patients with end-stage renal disease

  • Department of Nephrology, The Third People's Hospital of Bengbu, Bengbu Central Hospital, Bengbu Anhui 233000, China

  • Received Date: 2019-06-30
    Accepted Date: 2019-10-30
  • ObjectiveTo analyze the pulmonary artery pressure(PAP)of 128 end-stage renal disease(ESRD)patients treated with hemodialysis, investigate the occurrence of pulmonary artery hypertension(PAH)in patients with ESRD, and analyze the possible influencing factors of PAH.MethodsAmong 128 ESRD patients, 66 cases treated with hemodialysis and 62 cases without hemodialysis were divided into the observation group and control group, respectively.The PAH in two groups was evaluated by echocardiography, and the general data and echocardiographic results between two groups were compared.The observation group was subdivided into the non-PAH group and PAH group, the laboratory tests and cardiac ultrasound indicators were compared between two groups, and which was used to analyze the possible influencing factors of PAH.ResultsThe differences of the serum levels of creatinine, urea nitrogen, albumin, hemoglobin, blood calcium, blood phosphorus, 25(OH)D, intact parathyroid hormone(iPTH), and PAP between the observation group and control group were statistically significant(P < 0.05 to P < 0.01).The incidence rate of PAH in observation group(33.3%)was higher than that in control group(17.7%)(P < 0.05).The differences of the serum iPTH and hemodialysis time between PAH group and non-PAH group were statistically significant(P < 0.05 and P < 0.01).The differences of left atrial diameter, left ventricular end-diastolic diameter, left ventricular mass index and left ventricular ejection fraction between the PAH group and non-PAH group were statistically significant(P < 0.05).The results of unconditional logistic regression analysis showed that the left ventricular end-diastolic diameter, left atrial diameter, left ventricular mass index, left ventricular ejection fraction and(iPTH)were correlated the with occurrence of PAH(P < 0.05).ConclusionsPAH is common in patients with ESRD, and the incidence rate of which in long-term hemodialysis patients is higher, and the changes of left ventricular structure and function are closely related to PAH.
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  • [1] KAWAR B, ELIAM T, JACKSON C, et al. Pulmonary hypertension in renal disease: potential mechanisms and implications[J]. Am J Nephrol, 2013, 37(3): 281. doi: 10.1159/000348804
    [2] YIGLA M, FRUCHTER 0, AHARONSON D, et al. Pulmonary hypertension is an independent predictor of mortality in hemodialysis patients[J]. Kidney Int, 2009, 7(5): 969.
    [3] 周蓓蓓. 超声心动图在评价尿毒症患者心脏结构及功能改变中的应用[J]. 蚌埠医学院学报, 2015, 40(7): 956
    [4] AGARWAL R. Prevalence, determinants and prognosis of pulmonary hypertension among hemodialysis patients[J]. Nephrol Dial Transplant, 2015, 27(10): 3908.
    [5] YIGLA M, NAKHOUL F, SABAG A, et al. Pulmonary hypertension in patients with end stage renal disease[J]. Chest, 2003, 123(5): 1577. doi: 10.1378/chest.123.5.1577
    [6] REQUE J, QUIROGA B, RUIZ C, et al. Pulmonary hypertension is an independent predictor of cardiovascular events and mortality in haemodialysis patients[J]. Nephrology(Carlton), 2016, 21(4): 321.
    [7] LI Z, LIU S, SLIANG X, et al. Pulmonary hypertension as an independent predictor of cardiovascular mortality and events in hemodialysis patients[J]. Int Urol Nephrol, 2016, 46(1): 141.
    [8] PEACOCK AJ, MURPHY NF, MCMURRAY JJ, et al. An epidemigical study of pulmonary arterial hypertension[J]. Eur Respir J, 2007, 30(1): 104. doi: 10.1183/09031936.00092306
    [9] 贺艳军, 王玉玲, 李妙根, 等. 维持性血液透析患者发生肺动脉高压的风险因素分析[J]. 中华临床医师杂志, 2014, 8(12): 2264.
    [10] 潘敏, 金领微, 李占园, 等. 维持性血液透析患者发生肺动脉高压的危险因素分析[J]. 中国中西医结合肾病杂志, 2013, 14(6): 520. doi: 10.3969/j.issn.1009-587X.2013.06.016
    [11] 米爱红. 血液透析患者并发肺动脉高压的临床效果观察[J]. 中国医药指南, 2014, 6(13): 121.
    [12] 王娟. 血液透析对尿毒症患者肺动脉压产生的影响观察[J]. 世界中医药, 2015, 10(A01): 431.
    [13] NITTA K, AKIBA T, UCHIDA K, et al. The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis[J]. Am J Kidney Dis, 2003, 42(2): 303. doi: 10.1016/S0272-6386(03)00655-3
    [14] TAMOSIUNIENE R, TIAN W, DHILLON G, et al. Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension[J]. Circ Res, 2017, 109(8): 867.
    [15] SWAMJNATHAN S, SHAH SV. Novel inflammatory mechanisms of accelerated atherosclerosis in kidney disease[J]. Kidney Int, 2011, 80(5): 453. doi: 10.1038/ki.2011.178
    [16] 陈荣毅, 项方方, 胡家昌, 等. 维持性血液透析患者肺动脉高压与外周血CD8细胞比率降低相关[J]. 中华肾脏病杂志, 2017, 33(5): 342. doi: 10.3760/cma.j.issn.1001-7097.2017.05.004
    [17] 张颖, 夏思良. 超声心动图评估血液透析患者并发肺动脉高压的研究[J]. 中华全科医学, 2012, 10(4): 630.
    [18] 潘敏, 金领微, 李占园, 等. 维持性血液透析患者发生肺动脉高压的危险因素分析[J]. 中国中西医结合肾病杂志, 2013, 14(6): 520. doi: 10.3969/j.issn.1009-587X.2013.06.016
    [19] 杨文艳, 王建爽, 王艳辉, 等. 老年维持性血液透析患者肺动脉高压与超声心动图参数的相关性[J]. 实用老年医学, 2016, 11(30): 899.
    [20] 王艺萍, 赵娜, 刘煜, 等. 尿毒症难治性继发性甲状旁腺功能亢进症患者肺动脉压变化及其相关因素分析[J]. 兰州大学学报(医学版), 2014, 3(40): 17.
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Clinical study of pulmonary artery hypertension in patients with end-stage renal disease

  • Department of Nephrology, The Third People's Hospital of Bengbu, Bengbu Central Hospital, Bengbu Anhui 233000, China
  • Received Date: 2019-06-30
  • Accepted Date: 2019-10-30
  • Available Online: 2021-01-15

Abstract: ObjectiveTo analyze the pulmonary artery pressure(PAP)of 128 end-stage renal disease(ESRD)patients treated with hemodialysis, investigate the occurrence of pulmonary artery hypertension(PAH)in patients with ESRD, and analyze the possible influencing factors of PAH.MethodsAmong 128 ESRD patients, 66 cases treated with hemodialysis and 62 cases without hemodialysis were divided into the observation group and control group, respectively.The PAH in two groups was evaluated by echocardiography, and the general data and echocardiographic results between two groups were compared.The observation group was subdivided into the non-PAH group and PAH group, the laboratory tests and cardiac ultrasound indicators were compared between two groups, and which was used to analyze the possible influencing factors of PAH.ResultsThe differences of the serum levels of creatinine, urea nitrogen, albumin, hemoglobin, blood calcium, blood phosphorus, 25(OH)D, intact parathyroid hormone(iPTH), and PAP between the observation group and control group were statistically significant(P < 0.05 to P < 0.01).The incidence rate of PAH in observation group(33.3%)was higher than that in control group(17.7%)(P < 0.05).The differences of the serum iPTH and hemodialysis time between PAH group and non-PAH group were statistically significant(P < 0.05 and P < 0.01).The differences of left atrial diameter, left ventricular end-diastolic diameter, left ventricular mass index and left ventricular ejection fraction between the PAH group and non-PAH group were statistically significant(P < 0.05).The results of unconditional logistic regression analysis showed that the left ventricular end-diastolic diameter, left atrial diameter, left ventricular mass index, left ventricular ejection fraction and(iPTH)were correlated the with occurrence of PAH(P < 0.05).ConclusionsPAH is common in patients with ESRD, and the incidence rate of which in long-term hemodialysis patients is higher, and the changes of left ventricular structure and function are closely related to PAH.

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  • 肺动脉高压(pulmonary artery hypertension，PAH)指静息肺动脉压力(pulmonary artery pressure，PAP)>25 mmHg，或运动时PAP>35 mmHg。PAH分为原发性PAH和继发性PAH，前者是少见疾病，病因不明；后者常继发于心肺基础疾病或肺血管疾病。PAH按照2013年尼斯世界肺动脉高压大会标准可分5型：1型为内在血管疾病引起的PAH；2型与左心功能障碍相关；3型与呼吸系统疾病相关；4型为慢性血栓栓塞性肺PAH；5型为不明原因或多因素所致，包括慢性肾脏病(chronic kidney disease，CKD)或终末期肾病(end-stage renal disease，ESRD)所致[1]。近年研究[2]显示，PAH是CKD及ESRD病人常见并发症之一，且预后极差。检查PAP的方法[3]包括有创和无创检查，前者即右心导管测压，直观准确；后者包括超声心动图、肺功能、CT、核素扫描等，其中，超声心动图是最好的无创检查方法。本研究对ESRD及长期接受血液透析的ESRD病人PAH的发病情况、心脏超声指标及可能的病因进行分析。

1.   资料与方法

    1.1.   研究对象

  • 选取2015年1月至2017年12月在我院肾泌科住院病人128例，符合ESRD诊断标准：估算肾小球滤过率(eGFR)≤15 mL/min, 资料完整，其中男75例，女53例，年龄40~86岁；选取接受血液透析的ESRD病人66例作为观察组，其中原发疾病：慢性肾小球肾炎22例，糖尿病肾病23例，高血压肾损害14例，痛风性肾病3例，多囊肾病2例，慢性间质性肾炎1例，原发病不明1例。无血液透析病史的ESRD病人62例作为对照组，其中原发疾病：慢性肾小球肾炎18例，糖尿病肾病15例，高血压肾损害15例，痛风性肾病2例，多囊肾病2例，慢性间质性肾炎1例，原发病不明9例。2组病人原发病构成差异无统计学意义。排除标准：(1)重度左心瓣膜疾病相关性PAH史；(2)透析前有肺心病、原发性PAH、明确肺栓塞病史；(3)结缔组织病史；(4)肾移植术史。本研究经蚌埠市第三人民医院伦理委员会评议(伦科批字：2014-14)，属于回顾性研究，不再接触病人，豁免伦理程序。

    • 1.2.   方法

  • 血、尿、大便常规指标检测，肝肾功能、电解质、胸片等。全自动生化分析仪检测血清肌酐(Scr)、尿素氮(BUN)、尿酸(UA)、血钙(Ca)、血磷(P)、全段甲状旁腺激素(iPTH)，并计算eGFR。采用APLIO500型彩色多普勒仪(TOSHIBA公司)行心脏彩色多普勒检查，采用改良Simpson法测定左室舒张末期内径(LVEDD)、室间隔厚度(IVST)、左心室收缩末期内径(LVESD)、左室后壁舒张末期厚度(LVPW)、左室射血分数(LVEF)及最大血流速度比(E/A)，左心室质量指数(LVMI)。多普勒超声心动图测量肺动脉收缩压，估测肺动脉收缩压(PASP)。肺动脉压(PAP)=PASP+右心房压(5~10 cmH2O), 心房大小正常时，右心房压取5 mmHg；轻度增大时取10 mmHg。PAH定义为PAP≥35 mmHg[4]，并计算2组PAH的发生率。根据PAP值将观察组分为无PAH和PAH组，比较2组病人血清Scr、BUN、白蛋白(ALB)、血红蛋白(HB)、Ca、P、25(OH)D、全段甲状旁腺激素(iPTH)、PAP以及心脏超声指标，分析PAH发病的可能影响因素。

    • 1.3.   统计学方法

  • 采用t检验、检验和logistic回归分析。

2.   结果

    2.1.   观察组与对照组肝肾功能、电解质、iPTH、25(OH)D及PAH发生情况比较

  • 2组血清Scr、BUN、ALB、HB、Ca、P、25(OH)D、iPTH、PAP差异均有统计学意义(P < 0.05~P < 0.01)(见表 1)。观察组PAH发生率为33.3%(22/66)，高于对照组的17.7%(11/62)(χ2=4.06，P < 0.05)。

    分组 n Scr/(μmol/L) BUN/(mmol/L) ALB/(g/L) HB/(g/L) UA/(mmol/L) Ca/(μmol/L) P/(mmol/L) 25(OH)D/(ng/mL) iPTH/(g/L) PAP/mmHg
    观察组 66 837.52±69.23 23.03±3.46 36.11±2.98 96.09±16.16 336.08±60.75 2.39±0.28 2.23±0.28 19.82±8.12 326.89±68.50 34.86±6.80
    对照组 62 873.48±64.72 28.97±3.33 33.95±2.87 81.03±13.40 381.10±92.43 2.26±0.29 2.36±0.29 22.87±8.36 359.19±63.30 28.09±6.22
    t — 3.03 9.88 4.16 5.72 3.28 2.63 2.52 2.09 2.77 5.87
    P — < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.05 < 0.05 < 0.01 < 0.011

    • 2.2.   PAH组与无PAH组肝肾功能、电解质、iPTH、25(OH)D、血液透析时间比较

  • PAH组与无PAH组血清Scr、BUN、ALB、HB、Ca、P、25(OH)D差异均无统计学意义(P>0.05)，iPTH、血液透析时间差异有统计学意义(P < 0.05和P < 0.01)(见表 2)。

    分组 n SCR/(μmol/L) BUN/(mmol/L) ALB/(g/L)L HB/(g/L) P/(mmol/L) Ca/(μmol/L) 25(OH)D/(ng/mL) iPTH/(g/L) 透析时间/月
    PAH组 22 848.34±77.52 22.41±3.11 36.41±3.23 93.14±14.01 2.19±0.29 2.38±0.27 19.79±8.12 350.86±38.41 67.84±3.35
    无PAH组 44 832.11±64.97 23.34±3.61 35.95±2.88 97.57±17.10 2.25±0.27 2.36±0.25 19.85±8.46 309.91±25.95 68.53±2.68
    t — 0.89 1.03 0.58 1.05 0.78 0.29 0.02 2.29 15.98
    P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 < 0.05 < 0.01

    • 2.3.   PAH组与无PAH组超声心动图检测结果比较

  • PAH组与无PAH组的左心房内径、LVEDD、LVMI、LVEF差异均有统计学意义(P < 0.05)(见表 3)。

    分组 n LVEDD/mm IVST/mm LVESD/mm LVEF/% E/A 左心房内径/mm 右心房内径/mm 右心室内径/mm LVMI/mm
    PAH组 22 47.91±3.39 12.50±1.01 34.85±5.59 53.08±4.32 0.89±0.09 36.86±2.34 36.86±2.34 31.86±2.34 202.14±32.39
    无PAH组 44 46.09±3.38 12.57±1.04 33.88±5.94 56.85±5.48 0.91±0.13 41.09±1.48 36.11±1.43 31.27±1.42 141.11±53.96
    t — 2.05 0.25 0.63 2.82 0.70 4.57 1.63 1.27 4.87
    P — < 0.05 >0.05 >0.05 < 0.05 >0.05 < 0.05 >0.05 >0.05 < 0.05

    • 2.4.   观察组病人并发PAH的多因素回归分析

  • 非条件logistic回归分析结果显示，LVEDD、左心房内径、LVMI、LVEF、iPTH与PAH的发生有关(P < 0.05)(见表 4)。

    变量 B SE Waldχ2 P OR(95%CI)
    LVEDD 0.297 0.143 4.290 < 0.05 1.346(1.016~1.783)
    LVEF -0.171 0.084 4.130 < 0.05 0.843(0.715~0.994)
    左心房内径 0.996 0.371 7.194 < 0.05 2.708(1.308~5.608)
    LVMI 0.029 0.009 9.686 < 0.05 1.029(1.011~1.048)
    iPTH 0.042 0.016 6.891 < 0.05 1.043(1.011~1.076)
3.   讨论

  • PAH在CKD和ESRD病人中常见。根据诊断方法和CKD分期的不同，PAH的患病率为10%~70%，研究表明[5-8]PAH在CKD和ESRD病人中与不良结局的较高风险有关, ，维持性血液透析病人中，PAH的发生率为18.8%~68.8%，约是正常人的1万倍，合并有PAH病人的预后更差。这些病人并发PAH的原因，可能与以下因素有关：(1)动静脉内瘘所致的左向右分流，随着时间的推移，分流量逐渐增加，超出肺循环的调节能力，从而出现肺血管解剖及功能的改变; (2)贫血和容量负荷过多导致心脏负担加重; (3)长期高血压使左心功能障碍; (4)ESRD病人一氧化氮生成减少、血浆内皮素1水平增高、血栓素生成增多、前列环素生成减少，引起肺动脉阻力增加[9-12]; (5)甲状旁腺功能亢进、钙磷代谢紊乱在PAH的发生过程中也起着重要作用，可能与其促进血管钙化进程有关。钙亦可沉积在肺血管，肺动脉钙化导致肺毛细血管僵硬度增加，使肺循环阻力增加，引起PAH[13]; (6)尿毒症病人体内调节性T细胞减少可导致血管炎性反应，进而引起动脉粥样硬化，促进PAH形成[14-15]。近期的相关研究[16]亦发现维持性血液透析病人PAH与外周血CD8 T细胞比例降低有关。

    ESRD病人PAH发病率较高，本研究对照组PAH发病率为17.7%，观察组发病率为33.3%，观察组ESRD病人PAH发病率明显高于无透析组，说明动-静脉内瘘本身所致的心输出量增加、肺血流量增多可能会使PAP进一步升高[17]。观察组中PAH组左右心房内径、右心室内径、LVEDD、IVST、LVESD、LVMI均大于无PAH组，说明左心结构和功能异常是导致PAH的重要原因。同时，PAH组病人全段甲状旁腺激素水平高于无PAH组，提示PAH与甲状旁腺功能亢进密切相关。PAH组病人透析时间明显长于无PAH组，有学者[18]指出，ESRD病人病人随着透析时间的增长，肺血管解剖及功能改变，PAP随之呈现增高趋势。多因素回归分析显示LVEDD、左心房内径、LVMI、LVEF、iPTH水平与PAH的发生有关，慢性容量负荷过重亦与此相关，这与国内部分研究结论类似[19-20]。

    综上所述，ESRD病人PAH发生率较高，血液透析病人发生率更高，其主要原因与左心功能结构改变、慢性容量负荷过重有关，早期行彩色多普勒超声心动图检查以估测PAP，可以早期诊断ESRD相关PAH，目前PAH尚无可治愈手段，早期干预、充分血液透析可能会取得较好的治疗效果。

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