补体活化在原发性恶性高血压合并严重心肾损伤中的作用  

Role of complement activation in the pathogenesis of severe cardiorenal injury in patients with primary malignant hypertension

作　　者：徐潇漪[1] 孙丽君[1] 程虹[1] 董鸿瑞[1] 王国勤[1] 赵智睿 Xu Xiaoyi;Sun Lijun;Cheng Hong;Dong Hongrui;Wang Guoqin;Zhao Zhirui(Department of Nephrology,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院肾内科,北京100029

出　　处：《中华肾脏病杂志》2022年第2期115-125,共11页Chinese Journal of Nephrology

基　　金：国家自然科学基金(81900653);北京市自然科学基金(7192050、7194258)。

摘　　要：目的探讨补体活化在原发性恶性高血压(malignant hypertension,MHT)肾硬化症患者合并严重心肾损伤中的作用。方法回顾性收集2010年1月至2020年12月经首都医科大学附属北京安贞医院肾活检确诊为MHT肾硬化症患者的临床病理资料。免疫组化检测肾组织补体相关成分C4d、C1q、补体因子H相关蛋白5(CFHR⁃5)、C3c和C5b⁃9的表达。按照入选者是否合并急性心力衰竭和/或急性肾损伤分为严重心肾损伤组和非严重心肾损伤组,比较两组患者临床病理资料的差异。依据患者肾组织中补体活化指标C4d沉积情况分为C4d弥漫沉积组和非C4d弥漫沉积组,比较两组患者心、肾损伤程度及肾组织血栓性微血管病病变程度。结果33例MHT肾硬化症患者入选本研究,其中17例(51.5%)患者合并严重心肾损伤;16例(48.5%)患者发生急性心力衰竭,8例(26.7%)患者发生急性肾损伤,7例(21.2%)同时合并急性心力衰竭和急性肾损伤。与非严重心肾损伤组比较,严重心肾损伤组患者基线乳酸脱氢酶[326.0(217.0,366.0)IU/L比197.0(165.0,220.0)IU/L,Z=37.000,P=0.002]及血红蛋白[(143.6±24.0)g/L比(106.4±24.7)g/L,t=38.500,P<0.001]水平较高,禁水12 h尿渗透浓度[400.0(342.5,504.0)mmol/L比476.0(432.3,616.5)mmol/L,Z=72.000,P=0.021]和血清白蛋白[(36.2±9.4)g/L比(43.2±6.2)g/L,t=6.423,P=0.017]水平均较低,左心室后壁较厚[(14.0±2.1)mm比(12.1±1.1)mm,t=6.552,P=0.018]。肾组织免疫组化结果显示,严重心肾损伤组补体活化相关成分C4d及C5b⁃9弥漫沉积比例均高于非严重心肾损伤组(5/16比0/15,P=0.043;12/16比5/15,P=0.032)。与非C4d弥漫沉积组比较,C4d弥漫沉积组患者急性心力衰竭发生比例较高(5/5比10/26,P=0.018),心脏功能较差,心室重构较重,而高血压病史较短[2.0(0,12.0)个月比48.0(9.5,84.0)个月,Z=22.500,P=0.022]。结论MHT肾硬化症患者中严重心肾损伤的发生率约为51.5%,合并严重心肾损伤MHT患者肾组织补体活化�Objective To investigate the role of complement activation in the pathogenesis of primary malignant hypertension(MHT)with nephrosclerosis complicated with severe cardiorenal injury.Methods Data of MHT patients with nephrosclerosis proven by biopsy from January 2010 to December 2020 in the Beijing Anzhen Hospital,Capital Medical University were retrospectively analyzed.The expressions of complement⁃related component C4d,C1q,complement factor H⁃related protein 5,C3c and C5b⁃9 were detected by immunohistochemical staining.According to whether the patients were complicated with acute heart failure(AHF)and/or acute kidney injury(AKI),they were divided into severe cardiorenal injury group and non⁃severe cardiorenal injury group.The differences of clinicopathological data between the two groups were compared.According to the degree of C4d deposition in renal tissues,patients were divided into C4d diffused deposition group and non⁃C4d diffused deposition group.The severity of cardiorenal injury and the pathological characteristics of thrombotic microangiopathy in renal tissues were compared between the two groups.Results A total of 33 patients were enrolled in this study,of which 17 cases(51.5%)were complicated with severe cardiorenal injury;AHF occurred in 16 patients(48.5%),AKI occurred in 8 patients(26.7%),and AHF and AKI were combined in 7 patients(21.2%).Compared with non⁃severe cardiorenal injury group,patients in severe cardiorenal injury group had higher levels of baseline lactate dehydrogenase[326.0(217.0,366.0)IU/L vs 197.0(165.0,220.0)IU/L,Z=37.000,P=0.002]and hemoglobin[(143.6±24.0)g/L vs(106.4±24.7)g/L,t=38.500,P<0.001],lower levels of 12 h urinary incontinence osmolality[400.0(342.5,504.0)mmol/L vs 476.0(432.3,616.5)mmol/L,Z=72.000,P=0.021]and serum albumin[(36.2±9.4)g/L vs(43.2±6.2)g/L,t=6.423,P=0.017],and thicker left ventricular posterior wall[(14.0±2.1)mm vs(12.1±1.1)mm,t=6.552,P=0.018].The immunohistochemical results of kidney tissue showed that the proportions of C4d and C5b⁃9 diff

关 键 词：高血压 恶性 心力衰竭 急性肾损伤 心肾综合征 血栓性微血管病 补体激活 

分 类 号：R544.1[医药卫生—心血管疾病] R541.6[医药卫生—内科学] R692[医药卫生—临床医学]