恶性高血压相关临床研究

发布时间：2018-05-31 12:14

本文选题：恶性高血压 + 血栓性微血管病　；参考：《上海交通大学》2015年博士论文

【摘要】：目的:分析比较恶性高血压(MHT)患者的临床、肾脏病理、治疗及预后,了解MHT的疾病特点;对其中部分患者行血浆Adamts 13及补体因子检测以探究MHT的发病机制。方法:收集2004年1月至2014年12月上海交通大学医学院附属瑞金医院肾脏内科住院患者中临床确诊MHT者92例(包括单纯MHT者81例和MHT合并TMA者11例),回顾分析这些患者的临床、治疗及预后;分析其中74例肾活检者(包括单纯MHT者68例和MHT合并TMA者6例)的肾脏病理特点;对其中50例MHT患者及另外28例TMA患者,采用酶联免疫吸附测定(ELISA)法检测血浆Adamts 13活性、抗Adamts 13抗体浓度、CFH(补体H因子)浓度及MAC(补体攻膜复合物)浓度。结果:92例MHT中81例为单纯MHT(88.04%),11例(11.96%)为MHT合并TMA。单纯MHT组和MHT合并TMA组均以原发性MHT占大多数(90.12%和81.82%),既往有高血压病史者较多(50.62%和45.45%),均以肾脏受累症状起病为主(67.90%和54.54%),发病时血压明显升高(SBP:221.70 mm Hg和216.27 mm Hg,DBP:140.00 mm Hg和141.00 mm Hg)。单纯MHT组发病年龄偏大(35.00岁vs 30.00岁),男性患者比例高(83.95%vs 54.54%),BMI指数较高(26.40 kg/m2 vs 23.91 kg/m2)。MHT合并TMA组较MHT组肾功能严重减退(Scr:669.00μmol/l vs 287.00μmol/l,e GFR-EPI:8.10 ml?min-1?1.73m-2vs 22.20 ml?min-1?1.73m-2),血小板数明显减少(93.00×109/L vs 203.00×109/L),血红蛋白量显著下降(82.73 g/L vs 120.07 g/L),VWF升高(230.86%vs163.65%),并伴大量蛋白尿(尿常规示尿蛋白2+及以上)(100.00%vs 79.01%)。MHT治疗以多种降压药联合应用为主,其中MHT合并TMA组透析(血液透析或腹膜透析)率高(63.64%vs 12.34%)。经及时有效的治疗,单纯MHT组和MHT合并TMA组患者的预后较好,治愈率高(64.20%和81.82%),复发率低(6.17%和10.00%),但死亡率后者高于前者(0.00%vs 18.18%)。多因素生存分析提示女性(HR=2.730,P=0.017)、血清肌酐升高(HR=1.003,P0.001)是MHT肾脏预后的独立危险因素,而ACEI/ARB的应用(HR=0.393,P=0.040)能保护MHT患者的肾功能,延缓其进展。本组MHT患者肾活检率较高;单纯MHT组和MHT合并TMA组的肾活检率分别为83.94%和54.54%。两组患者病理特征均为中度肾小球硬化(硬化率≥50%)并伴中重度肾小管间质病变,大部分表现肾小血管纤维样增生(葱皮样改变)及透明样变性,且免疫荧光沉积均阴性;其中MHT合并TMA组还多伴有肾小血管内血栓形成(50.00%)。此外,MHT患者的肾小管间质病变严重程度与其血清肌酐水平呈正相关。检测的50例MHT患者中,32例(64.00%)血浆Adamts 13活性缺失者(酶活性5%),50例(100.00%)血浆抗Adamts 13抗体均阴性。44例单纯MHT者的血浆CFH浓度明显降低(462.13μg/m L),6例MHT合并TMA者的血浆CFH浓度正常(636.88μg/m L)。两组患者的血浆MAC浓度均明显升高(281.83ng/m L和288.89 ng/m L)。结论:本研究为国内大组MHT及相关性TMA的临床、病理及实验检测研究。MHT是临床危急重症,病情表现重,且发展迅速。多累及青壮年,眼、肾、心、脑为典型常见受累脏器。MHT可合并TMA,且MHT合并TMA者肾功能受累尤为严重。经积极及时有效的治疗干预,MHT疾病预后较好,存活率高,治愈率高,复发率低。本研究发现Adamts 13活性下降和补体旁路途径活化可能参与MHT的发病;血浆Adamts 13联合相关补体因子检测能较好地辅助MHT及相关性TMA的分层诊断。
[Abstract]:Objective: to analyze the clinical, renal pathology, treatment and prognosis of patients with malignant hypertension (MHT), to understand the disease characteristics of MHT, and to investigate the pathogenesis of Adamts 13 and complement factor in some of the patients to explore the pathogenesis of MHT. Methods: to collect the hospitalization of the Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2004 to December 2014. 92 patients with clinically confirmed MHT (including 81 patients with MHT and 11 MHT with TMA) were reviewed to analyze the clinical, treatment and prognosis of these patients, and to analyze the renal pathological features of 74 renal biopsy subjects (including 68 cases of MHT and 6 MHT with TMA), and 50 cases of MHT and 28 cases of TMA, using enzyme linked immunosorbent assay. The activity of plasma Adamts 13, the concentration of anti Adamts 13 antibody, the concentration of CFH (complement H factor) and the concentration of MAC (complement tapping complex) were detected by ELISA. Results: 81 cases of MHT in 92 cases were pure MHT (88.04%), 11 cases (11.96%) were MHT combined with TMA. simple MHT group and MHT combined group were the majority (90.12% and 81.82%), and had high blood before. There were more patients (50.62% and 45.45%) with the onset of renal involvement (67.90% and 54.54%), and blood pressure increased significantly (SBP:221.70 mm Hg and 216.27 mm Hg, DBP:140.00 mm Hg and 141 mm Hg). The age of the simple MHT group was higher (35 years of vs 30 years), and the proportion of male patients was higher (54.54%), and the index was higher (26.40 The renal function of M2 vs 23.91 kg/m2).MHT combined with TMA group was significantly lower than that in group MHT (Scr:669.00 mu mol/l vs 287 micron mol/l, e GFR-EPI:8.10), and the number of platelets decreased significantly (93 * 203 * 203), and the amount of hemoglobin decreased significantly. A large number of albuminuria (urine routine urinary protein 2+ and above) (100.00%vs 79.01%) (100.00%vs 79.01%) was used in combination with a variety of hypotensive drugs. The rate of MHT combined with TMA group (hemodialysis or peritoneal dialysis) was high (63.64%vs 12.34%). After timely and effective treatment, the prognosis of patients with simple MHT group and MHT combined with TMA group was better (64.20% and 81.). 82%), the recurrence rate was low (6.17% and 10%), but the mortality rate was higher than that of the former (0.00%vs 18.18%). Multiple factor survival analysis suggested that women (HR=2.730, P=0.017), serum creatinine (HR=1.003, P0.001) were independent risk factors for MHT renal prognosis, and ACEI/ARB should be used (HR=0.393, P=0.040) to protect the renal function of MHT patients and postpone its progress. The renal biopsy rate of MHT patients was higher. The renal biopsy rates in group MHT and group TMA were 83.94% and 54.54%. two, respectively, and the pathological features were moderate glomerulosclerosis (sclerotic rate > 50%) and moderate to severe tubulointerstitial lesions, most of which showed renal small vascular fibroid hyperplasia (scallion dermoid change) and hyaline degeneration, and immunofluorescence precipitation. The product was negative, among which MHT combined with TMA was accompanied by small intravascular thrombus formation (50%). In addition, the severity of renal tubulointerstitial lesions in MHT patients was positively correlated with serum creatinine levels. In 50 MHT patients, 32 cases (64%) had plasma Adamts 13 activity deficiency (enzyme activity 5%), 50 cases (100%) of plasma anti Adamts 13 antibody was negative. The plasma CFH concentration in.44 patients with simple MHT was significantly decreased (462.13 g/m L), and the plasma CFH concentration in 6 cases with TMA was normal (636.88 mu g/m L). The plasma MAC concentration in group two was significantly increased (281.83ng/m and 288.89). The bed is critical and severe, and its condition is heavy and developing rapidly. The typical common affected organs.MHT can be combined with TMA in the eyes, kidney, heart and brain, and the renal function of MHT combined with TMA is especially serious. After active and effective treatment, the prognosis of MHT is better, the survival rate is high, the cure rate is high, and the recurrence rate is low. This study found Adamts 13 live. The reduction of sex and the activation of complement pathway may be involved in the pathogenesis of MHT, and the detection of plasma Adamts 13 combined with related complement factor can better assist the stratified diagnosis of MHT and associated TMA.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R544.1

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