慢性肾脏病患者血清妊娠相关血浆蛋白-A水平与颈动脉内中膜厚度的关系
发布时间：2018-08-26 11:03
【摘要】：目的:检测慢性肾脏病(Chronic kidney disease,CKD)患者血清妊娠相关血浆蛋白-A(Pregnancy-Associated Plasma Protein-A,PAPP-A)、超敏C反应蛋白(high sensitive-C-reactive protein,Hs-CRP)水平的变化和颈动脉超声,分析CKD患者PAPP-A与颈动脉内中膜厚度(intima-media thickness,IMT)的相关性及其影响因素。方法:1实验组:选取2014年1月至2014年8月在河北医科大学第二医院肾内科住院的非透析CKD患者71例,男性44例,女性27例,年龄20~68岁,平均年龄44.95±12.86岁,原发病分别为慢性肾小球肾炎69例,成人常染色体显性遗传性多囊肾2例。根据CKD-EPI公式,计算肾小球滤过率(e GRF[ml/min/1.73m2])进行分组,将CKD患者分为CKD3期、CKD4期和CKD5期组。其中,CKD3期组24例,男14例,女10例,年龄42.17±13.55岁,CKD4期组17例,男14例,女3例,年龄47.44±11.31岁,CKD5期组30例,男16例,女14例,年龄46.79±13.24岁。排除标准:(1)3个月内发生急性感染或创伤,(2)慢性肾功能不全急性加重,(3)结缔组织病,(4)糖尿病肾病,(5)家族性高脂血症,(6)入选前3个月使用过激素或免疫抑制剂治疗,(7)妊娠或分娩,(8)入选前3个月内发生急性心脑血管事件,(9)高尿酸血症,另选取同期我院体检中心的健康体检者16例为对照组,其中男性7人,女性9人,年龄47.31±10.42岁。2采用酶联免疫吸附试验(ELISA)方法检测PAPP-A的浓度,免疫比浊法测定Hs-CRP的浓度,采用飞利浦IE33彩色多普勒超声检测仪检测患者颈动脉内膜中层厚度IMT及斑块。连续测量2个心动周期,取其平均值作为颈动脉IMT值,IMT1.0mm为正常,IMT≥1.0 mm视为早期动脉粥样硬化,IMT≥1.2mm或局部呈混合回声或强回声则为有斑块形成。同时测定血常规、肝功能、肾功能、血脂和甲状旁腺激素(IPTH)等生化指标,并记录患者一般资料:性别、年龄、原发病、既往有无心血管疾病史、血压、体质量指数(BMI)、吸烟史等。3采用SPSS13.0软件对数据进行统计学分析,取α=0.05为检验水准,以P0.05为差异,代表有统计学意义。结果:1 CKD患者血清PAPP-A和Hs-CRP水平:CKD患者血清PAPP-A水平[63.24(62.14)ng/ml]较对照组[24.26(22.25)ng/ml]明显升高(P0.01)。CKD3、4、5期患者血清PAPP-A水平分别为38.13(38.85)ng/ml、61.69(61.20)ng/ml、84.20(88.00)ng/ml,均较对照组显著升高,差异有统计学意义(P均0.01)。且随着肾功能的恶化血PAPP-A呈进行性升高。CKD患者血清Hs-CRP水平为[11.14(12.03)mg/L]较对照组[3.15(3.02)mg/L]显著升高(P0.01),CKD3、4、5期患者血清Hs-CRP水平分别为7.17(7.15)mg/L、11.04(10.98)mg/L、14.37(15.12)mg/L。组间比较结果显示,CKD4期组明显高于CKD3期组,差异有统计学意义(P均0.01),CKD5期组分别高于CKD3期组和CKD4期组(P0.01)。2 CKD患者颈动脉超声检测结果:CKD患者颈动脉硬化(IMT≥1.0mm和(或)斑块形成)发生率(25.30%)显著高于对照组(18.8%),差异有统计学意义(P0.05)。CKD3、4、5期患者颈动脉硬化发生率分别为:20.8%、35.3%和36.7%。组间比较结果显示,CKD5期组和CKD4期组明显高于CKD3期组,差异有统计学意义(P0.05)。CKD患者颈动脉脉内膜中层厚度(IMT)为[0.86(0.80)mm]较对照组IMT值[0.66(0.60)mm]明显增厚(P0.05)。CKD3、4、5期患者颈动脉IMT分别为0.83(0.70)mm、0.85(0.80)mm、0.86(0.80)mm,其中CKD4期和CKD5期较对照组IMT值明显增厚,差异有统计学意义(P值均0.05)。3 CKD患者血清PAPP-A和Hs-CRP浓度与颈动脉硬化的关系:按照颈动脉超声检测结果,分为颈动脉正常组(IMT1.0mm)和颈动脉硬化[IMT≥1.0mm,和(或)斑块形成]组。CKD伴颈动脉硬化组血清PAPP-A水平[78.28(89.45)ng/ml]较无颈动脉硬化组[56.48(58.20)ng/ml]明显升高(P0.01)。CKD伴颈动脉硬化组血清Hs-CRP水平[12.91(13.63)mg/L]较无颈动脉硬化组[10.34(10.10)mg/L]明显升高(P0.01)。4 CKD患者血清PAPP-A水平和颈动脉IMT与微炎症状态的关系:按hs-CRP水平将CKD患者分为hs-CRP≥8mg/L组和hs-CRP8mg/L组,hs-CRP≥8mg/L组PAPP-A[70.75(70.60)ng/ml]及IMT[0.89(0.80)mm]水平较hs-CRP8mg/L组[PAPP-A 35.20(35.40)ng/ml,IMT 0.76(0.70)mm]明显升高,差异有统计学意义(P值均0.01)。5相关分析结果:①IMT与PAPP-A(r=0.521,P0.001)、Hs-CRP(r=0.456,P0.001)成显著正相关。②PAPP-A与hs-CRP成正显著相关(r=0.955,P0.01)。PAPP-A水平与血红蛋白(r=-0.651,P0.01)、白蛋白(r=-0.4.6,P0.01)、体重指数(r=-0.564,P0.01)成负相关。PAPP-A水平收缩压(r=0.342,P0.01)、尿素氮(r=0.7.1,P0.01)、血肌酐(r=0.666,P0.01)、血尿酸(r=0.241,P0.01)成显著正相关。③Hs-CRP与血肌酐(r=0.689,P0.01)正相关。Hs-CR水平与与体重指数(r=-0.564,P0.001)、血红蛋白(r=-0.721,P0.01)、白蛋白(r=-0.491,P0.01)呈负相关。收缩压(r=0.342,P0.001)、尿素氮(r=0.752,P0.01)血肌酐(r=0.689,P0.01)、血尿酸(r=0.295,P0.01)、血甲状旁腺激素(r=0.321,P0.01)成正相关。6多元线性回归分析显示:①hs-CRP(β=0.006,P0.01),PAPP-A(β=0.007,P0.001),Scr(β=0.0244,P0.05),Hb(β=0.003,P0.05)是颈动脉IMT的显著相关因素。结论:1 CKD患者血清PAPP-A和Hs-CRP与颈动脉硬化密切相关。2 CKD患者血清PAPP-A是颈动脉硬化的独立危险因子。3血清PAPP-A与Hs-CRP可能与炎症共同参与了CKD患者动脉粥样硬化的发生和发展。4检测血PAPP-A、hs-CRP浓度联合颈动脉超声,可以作为判断CKD患者动脉粥样硬化病变的程度的指标。
[Abstract]:Objective: To detect the changes of serum levels of pregnancy-associated plasma protein-A (PAPP-A), high sensitive C-reactive protein (Hs-CRP) and carotid artery ultrasonography in patients with chronic kidney disease (CKD), and to analyze the relationship between PAPP-A and intima-media thickness (intima-media t) in patients with CKD. Methods: 1 Experimental group: From January 2014 to August 2014, 71 non-dialysis CKD patients, 44 males and 27 females, aged 20-68 years, with an average age of 44.95 [12.86], were enrolled in the Department of Nephrology, Second Hospital of Hebei Medical University. According to the CKD-EPI formula, the glomerular filtration rate (e GRF [ml/min/1.73m2]) was calculated and divided into CKD stage 3, CKD stage 4 and CKD stage 5 groups. There were 24 patients in CKD stage 3 group, 14 males and 10 females, aged 42.17+13.55 years, 17 patients in CKD stage 4 group, 14 males and 3 females, aged 47.44+11.31 years, 30 patients in CKD stage 5 group, 16 males and 10 females. Fourteen women, aged 46.79 [13.24], were excluded from the study. The criteria were: (1) acute infection or trauma within three months, (2) acute exacerbation of chronic renal insufficiency, (3) connective tissue disease, (4) diabetic nephropathy, (5) familial hyperlipidemia, (6) steroid or immunosuppressive therapy three months before enrollment, (7) pregnancy or childbirth, (8) acute onset within three months before enrollment. Cardiovascular and cerebrovascular events (9) Hyperuricemia. Sixteen healthy volunteers from the physical examination center of our hospital at the same time were selected as control group, including 7 males and 9 females, aged 47.31 [10.42]. 2 The concentration of PAPP-A was detected by enzyme-linked immunosorbent assay (ELISA), the concentration of Hs-CRP was determined by immunoturbidimetry, and the concentration of Hs-CRP was detected by Philips IE33 color Doppler ultrasonography. IMT and plaque were measured by echocardiograph. Two cardiac cycles were measured continuously. The mean IMT was taken as carotid IMT value. IMT 1.0 mm was normal. IMT (>1.0 mm) was regarded as early atherosclerosis. IMT (>1.2 mm) or local mixed echo or strong echo was considered as plaque formation. Blood routine, liver function and renal function were also measured. Can, blood lipids and parathyroid hormone (IPTH) and other biochemical indicators, and records of patients with general information: gender, age, primary disease, history of cardiovascular disease, blood pressure, body mass index (BMI), smoking history, etc. 3 using SPSS 13.0 software for statistical analysis of the data, taking alpha = 0.05 as the test level, with P 0.05 as the difference, on behalf of statistical significance. Results: 1 Serum PAPP-A and Hs-CRP levels in patients with CKD: The serum PAPP-A levels in patients with CKD [63.24 (62.14) ng/ml] were significantly higher than those in the control group [24.26 (22.25) ng/ml] (P 0.01). The serum PAPP-A levels in patients with CKD 3, 4 and 5 were 38.13 (38.85) ng/ml, 61.69 (61.20) ng/ml, 84.20 (88.00) ng/ml, respectively, which were significantly higher than those in the control group (P 0.05). The serum levels of Hs-CRP in CKD patients were 11.14 (12.03) mg/L and 7.17 (7.15) mg/L, 11.04 (10.98) mg/L, 14.37 (15.12) mg/L, respectively, in CKD stage 3, 4 and 5, compared with CKD control group [3.15 (3.02) mg/L] (P 0.01). The incidence of carotid atherosclerosis (IMT < 1.0mm and/or plaque formation) in CKD patients (25.30%) was significantly higher than that in CKD patients (18.8%) and the difference was statistically significant (P 0.05). The carotid atherosclerosis rate in CKD patients (P 0.01) was significantly higher than that in CKD patients (P 0.05). The incidence of carotid intima-media thickness (IMT) in CKD patients was 0.86 (0.80) mm, which was significantly thicker than that in control group (0.66 (0.60) mm). The IMT in CKD5, CKD4 and CKD3 was 0.8 mm, respectively. 3 (0.70) mm, 0.85 (0.80) mm, 0.86 (0.80) mm, in which CKD4 and CKD5 were significantly thicker than the control group IMT values, the difference was statistically significant (P values were 0.05). 3 The relationship between serum PAPP-A and Hs-CRP levels and carotid atherosclerosis in patients with CKD: According to the results of carotid ultrasonography, patients were divided into normal carotid artery group (IMT 1.0 mm) and carotid atherosclerosis [IMT < 1.0 mm, and (IMT < 1.0 mm, and < 1.0 mm The serum levels of PAPP-A in CKD patients with carotid atherosclerosis [78.28 (89.45) ng/ml] were significantly higher than those in non-carotid atherosclerosis group [56.48 (58.20) ng/ml] (P 0.01). The serum levels of Hs-CRP [12.91 (13.63) mg/L] in CKD patients with carotid atherosclerosis were significantly higher than those in non-carotid atherosclerosis group [10.34 (10.10) mg/L] (P 0.01). Relationship between carotid IMT and Micro-inflammatory state: According to hs-CRP level, CKD patients were divided into hs-CRP (> 8mg/L) group and hs-CRP 8mg/L group. The levels of PAPP-A [70.75 (70.60) ng/ml] and IMT [0.89 (0.80) mm] in hs-CRP group were significantly higher than those in hs-CRP 8mg/L group [PAPP-A 35.20 (35.40) ng/ml, IMT 0.76 (0.70) mm], with significant difference (P 0.01). Results: 1) IMT was positively correlated with PAPP-A (r = 0.521, P 0.001), Hs-CRP (r = 0.456, P 0.001) and Hs-CRP (r = 0.456, P 0.001) significantly positively correlated with PAPP-A and hs-CRP (r = 0.955, P 0.01). The levels of PAPP-A and hemoglobin (r =-0.651, P 0.01), album (r =-0.0.4.6, P 0.01, P 0.01), body mass index (r =-0.564, P 0.564, P 0.01) negatively correlwith systolic pressure (r = PAPP-A level systolic pressure (r = 0.PAPP-Urea nitrogen (r = 0.7). (3) Hs-CRP was positively correlated with sercreatinine (r = 0.689, P 0.01). Hs-CRP was positively correlated with body mass index (r = - 0.564, P 0.001), hemoglobin (r = - 0.721, P 0.01), albumin (r = - 0.721, P 0.01), albumin (r = - 0.491, P 0.01) was negatively correlwith systostolicpressure (r = 0.342, P 0.001), ureanitrogen (ureanitrogen (ureanitrogen (r = 0.001), ureanitrogen (ureanitrogen (r = 0.752, ureanitrogen (r = 0.752, ureanitrogen (r = 0.752, 0.752, 0.752 01) serum creatinine (r= Multivariate linear regression analysis showed that: (1) hs-CRP (beta = 0.006, P 0.01), PAPP-A (beta = 0.007, P 0.001), Scr (beta = 0.0244, P 0.05), Hb (beta = 0.003, IMP 0.05) were significantly correlated with carotid artery stiffness. Serum PAPP-A is an independent risk factor for carotid atherosclerosis in patients with CKD. 3 Serum PAPP-A and Hs-CRP may participate in the occurrence and development of atherosclerosis in patients with CKD together with inflammation.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R692
本文编号：2204674
[Abstract]:Objective: To detect the changes of serum levels of pregnancy-associated plasma protein-A (PAPP-A), high sensitive C-reactive protein (Hs-CRP) and carotid artery ultrasonography in patients with chronic kidney disease (CKD), and to analyze the relationship between PAPP-A and intima-media thickness (intima-media t) in patients with CKD. Methods: 1 Experimental group: From January 2014 to August 2014, 71 non-dialysis CKD patients, 44 males and 27 females, aged 20-68 years, with an average age of 44.95 [12.86], were enrolled in the Department of Nephrology, Second Hospital of Hebei Medical University. According to the CKD-EPI formula, the glomerular filtration rate (e GRF [ml/min/1.73m2]) was calculated and divided into CKD stage 3, CKD stage 4 and CKD stage 5 groups. There were 24 patients in CKD stage 3 group, 14 males and 10 females, aged 42.17+13.55 years, 17 patients in CKD stage 4 group, 14 males and 3 females, aged 47.44+11.31 years, 30 patients in CKD stage 5 group, 16 males and 10 females. Fourteen women, aged 46.79 [13.24], were excluded from the study. The criteria were: (1) acute infection or trauma within three months, (2) acute exacerbation of chronic renal insufficiency, (3) connective tissue disease, (4) diabetic nephropathy, (5) familial hyperlipidemia, (6) steroid or immunosuppressive therapy three months before enrollment, (7) pregnancy or childbirth, (8) acute onset within three months before enrollment. Cardiovascular and cerebrovascular events (9) Hyperuricemia. Sixteen healthy volunteers from the physical examination center of our hospital at the same time were selected as control group, including 7 males and 9 females, aged 47.31 [10.42]. 2 The concentration of PAPP-A was detected by enzyme-linked immunosorbent assay (ELISA), the concentration of Hs-CRP was determined by immunoturbidimetry, and the concentration of Hs-CRP was detected by Philips IE33 color Doppler ultrasonography. IMT and plaque were measured by echocardiograph. Two cardiac cycles were measured continuously. The mean IMT was taken as carotid IMT value. IMT 1.0 mm was normal. IMT (>1.0 mm) was regarded as early atherosclerosis. IMT (>1.2 mm) or local mixed echo or strong echo was considered as plaque formation. Blood routine, liver function and renal function were also measured. Can, blood lipids and parathyroid hormone (IPTH) and other biochemical indicators, and records of patients with general information: gender, age, primary disease, history of cardiovascular disease, blood pressure, body mass index (BMI), smoking history, etc. 3 using SPSS 13.0 software for statistical analysis of the data, taking alpha = 0.05 as the test level, with P 0.05 as the difference, on behalf of statistical significance. Results: 1 Serum PAPP-A and Hs-CRP levels in patients with CKD: The serum PAPP-A levels in patients with CKD [63.24 (62.14) ng/ml] were significantly higher than those in the control group [24.26 (22.25) ng/ml] (P 0.01). The serum PAPP-A levels in patients with CKD 3, 4 and 5 were 38.13 (38.85) ng/ml, 61.69 (61.20) ng/ml, 84.20 (88.00) ng/ml, respectively, which were significantly higher than those in the control group (P 0.05). The serum levels of Hs-CRP in CKD patients were 11.14 (12.03) mg/L and 7.17 (7.15) mg/L, 11.04 (10.98) mg/L, 14.37 (15.12) mg/L, respectively, in CKD stage 3, 4 and 5, compared with CKD control group [3.15 (3.02) mg/L] (P 0.01). The incidence of carotid atherosclerosis (IMT < 1.0mm and/or plaque formation) in CKD patients (25.30%) was significantly higher than that in CKD patients (18.8%) and the difference was statistically significant (P 0.05). The carotid atherosclerosis rate in CKD patients (P 0.01) was significantly higher than that in CKD patients (P 0.05). The incidence of carotid intima-media thickness (IMT) in CKD patients was 0.86 (0.80) mm, which was significantly thicker than that in control group (0.66 (0.60) mm). The IMT in CKD5, CKD4 and CKD3 was 0.8 mm, respectively. 3 (0.70) mm, 0.85 (0.80) mm, 0.86 (0.80) mm, in which CKD4 and CKD5 were significantly thicker than the control group IMT values, the difference was statistically significant (P values were 0.05). 3 The relationship between serum PAPP-A and Hs-CRP levels and carotid atherosclerosis in patients with CKD: According to the results of carotid ultrasonography, patients were divided into normal carotid artery group (IMT 1.0 mm) and carotid atherosclerosis [IMT < 1.0 mm, and (IMT < 1.0 mm, and < 1.0 mm The serum levels of PAPP-A in CKD patients with carotid atherosclerosis [78.28 (89.45) ng/ml] were significantly higher than those in non-carotid atherosclerosis group [56.48 (58.20) ng/ml] (P 0.01). The serum levels of Hs-CRP [12.91 (13.63) mg/L] in CKD patients with carotid atherosclerosis were significantly higher than those in non-carotid atherosclerosis group [10.34 (10.10) mg/L] (P 0.01). Relationship between carotid IMT and Micro-inflammatory state: According to hs-CRP level, CKD patients were divided into hs-CRP (> 8mg/L) group and hs-CRP 8mg/L group. The levels of PAPP-A [70.75 (70.60) ng/ml] and IMT [0.89 (0.80) mm] in hs-CRP group were significantly higher than those in hs-CRP 8mg/L group [PAPP-A 35.20 (35.40) ng/ml, IMT 0.76 (0.70) mm], with significant difference (P 0.01). Results: 1) IMT was positively correlated with PAPP-A (r = 0.521, P 0.001), Hs-CRP (r = 0.456, P 0.001) and Hs-CRP (r = 0.456, P 0.001) significantly positively correlated with PAPP-A and hs-CRP (r = 0.955, P 0.01). The levels of PAPP-A and hemoglobin (r =-0.651, P 0.01), album (r =-0.0.4.6, P 0.01, P 0.01), body mass index (r =-0.564, P 0.564, P 0.01) negatively correlwith systolic pressure (r = PAPP-A level systolic pressure (r = 0.PAPP-Urea nitrogen (r = 0.7). (3) Hs-CRP was positively correlated with sercreatinine (r = 0.689, P 0.01). Hs-CRP was positively correlated with body mass index (r = - 0.564, P 0.001), hemoglobin (r = - 0.721, P 0.01), albumin (r = - 0.721, P 0.01), albumin (r = - 0.491, P 0.01) was negatively correlwith systostolicpressure (r = 0.342, P 0.001), ureanitrogen (ureanitrogen (ureanitrogen (r = 0.001), ureanitrogen (ureanitrogen (r = 0.752, ureanitrogen (r = 0.752, ureanitrogen (r = 0.752, 0.752, 0.752 01) serum creatinine (r= Multivariate linear regression analysis showed that: (1) hs-CRP (beta = 0.006, P 0.01), PAPP-A (beta = 0.007, P 0.001), Scr (beta = 0.0244, P 0.05), Hb (beta = 0.003, IMP 0.05) were significantly correlated with carotid artery stiffness. Serum PAPP-A is an independent risk factor for carotid atherosclerosis in patients with CKD. 3 Serum PAPP-A and Hs-CRP may participate in the occurrence and development of atherosclerosis in patients with CKD together with inflammation.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R692
【参考文献】
相关期刊论文 前2条
1 唐湘玲;陈梦颖;张卫茹;;慢性肾脏病患者血清内脏脂肪素水平升高及其与颈动脉粥样硬化的关系(英文)[J];中南大学学报(医学版);2013年06期
2 夏斌;徐江祥;黄小红;帅记焱;王霞;;颈动脉粥样硬化与冠心病的相关性研究[J];医学信息(中旬刊);2011年07期
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