CAJ | 학술논문

目的对IgA肾病(IgAN)患者的临床及病理资料进行分析,旨在探讨补体活化在IgAN中的意义,为临床治疗提供依据.方法回顾性分析本院确诊的原发性IgAN患者,记录患者基线一般情况、临床指标、病理学检查及随访结果.根据免疫荧光下补体C3在系膜区沉积情况,分为阴性、弱阳性、强阳性3组,血C3降低组的定义为血清C3＜ 85 mg/dl.结果本研究纳入528例患者,平均随访3年.肾组织C3沉积阴性组、弱阳性组、强阳性组患者分别为119例(22.5％)、164例(31.1％)和245例(46.4％);血C3降低组患者93例(21.7％),血C3正常组335例(78.3％);系膜区C3沉积与血清C3水平呈负相关(r=-0.209,P＜0.01);不同肾组织C3沉积组间年龄、性别差异无统计学意义;随肾组织C3沉积加重,患者基线血肌酐、尿酸、血IgA水平升高,估算肾小球滤过率(eGFR)、体质量指数(BMI)降低(P＜0.05),C3沉积较多的患者肾组织毛细血管内细胞增生和肾小管萎缩、肾间质纤维化更为严重(P＜ 0.05).与血C3正常组比较,血C3降低组患者白细胞、血红蛋白、三酰甘油、胆固醇、eGFR水平较低,而血肌酐水平较高(P＜0.05).随访期间,共有54例患者进入终末期肾病(ESRD),血C3降低组ESRD发生率为23.7％,正常组为8.4％,Kaplan-Meier分析显示血C3降低组肾脏中位生存时间显著低于C3正常组[(145.0±22.5)个月比(150.8±17.0)个月,P＜0.01].Cox回归分析显示,校正性别、年龄和临床指标(平均动脉压、eGFR、白蛋白、尿蛋白、血红蛋白水平)后,血清C3降低(HR=0.97,95％CI 0.96,0.99,P＜0.01)为患者进入ESRD的独立危险因素.结论 IgAN患者存在不同程度补体系统活化,补体活化与患者基础肾功能及临床预后相关,血清C3下降为患者进入ESRD的独立危险因素,提示补体活化可能参与IgAN的进程.
목적 대IgA신병(IgAN)환자적림상급병리자료진행분석,지재탐토보체활화재IgAN중적의의,위림상치료제공의거.방법 회고성분석본원학진적원발성IgAN환자,기록환자기선일반정황、림상지표、병이학검사급수방결과.근거면역형광하보체C3재계막구침적정황,분위음성、약양성、강양성3조,혈C3강저조적정의위혈청C3＜ 85 mg/dl.결과 본연구납입528례환자,평균수방3년.신조직C3침적음성조、약양성조、강양성조환자분별위119례(22.5％)、164례(31.1％)화245례(46.4％);혈C3강저조환자93례(21.7％),혈C3정상조335례(78.3％);계막구C3침적여혈청C3수평정부상관(r=-0.209,P＜0.01);불동신조직C3침적조간년령、성별차이무통계학의의;수신조직C3침적가중,환자기선혈기항、뇨산、혈IgA수평승고,고산신소구려과솔(eGFR)、체질량지수(BMI)강저(P＜0.05),C3침적교다적환자신조직모세혈관내세포증생화신소관위축、신간질섬유화경위엄중(P＜ 0.05).여혈C3정상조비교,혈C3강저조환자백세포、혈홍단백、삼선감유、담고순、eGFR수평교저,이혈기항수평교고(P＜0.05).수방기간,공유54례환자진입종말기신병(ESRD),혈C3강저조ESRD발생솔위23.7％,정상조위8.4％,Kaplan-Meier분석현시혈C3강저조신장중위생존시간현저저우C3정상조[(145.0±22.5)개월비(150.8±17.0)개월,P＜0.01].Cox회귀분석현시,교정성별、년령화림상지표(평균동맥압、eGFR、백단백、뇨단백、혈홍단백수평)후,혈청C3강저(HR=0.97,95％CI 0.96,0.99,P＜0.01)위환자진입ESRD적독립위험인소.결론 IgAN환자존재불동정도보체계통활화,보체활화여환자기출신공능급림상예후상관,혈청C3하강위환자진입ESRD적독립위험인소,제시보체활화가능삼여IgAN적진정.
Objective To explore the clinical significance of complement activation in IgA nephropathy (IgAN) patients and provide new potential therapy targets.Methods Biopsy-proven IgAN patients admitted in our renal center were retrospectively recruited.Demographic,baseline clinical and pathological data were recorded as well as the follow-up results.Patients were divided into three groups,negative,weak positive and strong positive group,according to the intensity of C3 deposition in mesangial area of glomurili.Decreased serum C3 level was defined as C3 ＜ 85 mg/dl.Results In this study,528 IgAN patients were recruited and mean follow-up time was 3 years.There were 119 (22.5％),164(31.1％),245(46.4％) patients in the negative,weak positive and strong positive group respectively; 93(21.7％) patients had decreased serum C3 level and 335(78.3％) patients had normal serum C3 level; Significant negative correlation was found between mesangial area of C3 deposition and serum level of C3(r =-0.209,P ＜ 0.01).The age or sex were similar among different groups of mesangial C3 deposition.In univariate analysis,higher baseline serum creatinine,uric acid and IgA levels,and lower estimated glomerular filtration rate(eGFR),body mass index (BMI) levels were associated with a higher grade of mesangial C3 deposition (P ＜ 0.05).Endocapillary hypercellularity and tubular atrophy or interstitial fibrosis were more prominent in patients with higher grade mesangial deposition of C3.Compared with the patients with normal serum C3 level,patients with decreased serum C3 level had lower white blood cells,hemoglobin,triglyceride,cholesterol,eGFR level and higher serum creatinine level (P ＜ 0.05).During the follow-up,a total of 54 patients developed to end stage renal disease (ESRD),the incidence of ESRD was 23.7％ in patients with decreased serum C3 level and 8.4％ with normal C3 level.Kaplan-Meier analysis showed that median outcome-free survival time of patients with decreased serum C3 level was significant shorter than patients with normal serum C3 level [(145.0±22.5) months vs (150.8± 17.0) months,P ＜ 0.01].Cox regression proportional hazards models showed that after adjusting by sex,age and clinical indicators (MAP,eGFR,serum albumin,urine protein and hemoglobin level),decreased serum C3 level (HR =0.97,95％ CI 0.96,0.99,P＜ 0.01)remained be an independent risk factor of ESRD.Conclusions There are different levels of complement activation in patients with IgAN.Complement activation is associated with baseline renal function and clinical outcomes,and decreased serum C3 level is an independent risk factor of ESRD in IgAN patients.Complement activation may be involved in the progression of IgAN.