慢性移植肾肾病肾间质非特异性细胞浸润的意义

目的 探讨不同类型慢性移植肾肾病组织非特异性细胞浸润的意义及其预后.方法 回顾性分析2007年6月至2009年6月间83例肾移植受者的资料,受者均经移植肾穿刺证实为慢性移植肾肾病(CAN).按照Banff 2009标准,病例分为3组:慢性活动性T淋巴细胞介导的排斥反应(CTMR)组、慢性活动性抗体介导的排斥反应(CAMR)组和无特异性的间质纤维化和肾小管萎缩(NOS)组.检测并分析移植肾组织中肾小管和肾间质病变程度,CD4+、CD8+、CD20+和CD3+细胞浸润以及补体C4d染色情况.随访2年,记录移植肾存活率.结果 CTMR组受者为34例(40.9％),CAMR组为12例(14.6％),NOS组为37例(44.5％).3组间质炎症浸润范围、管周毛细血管炎和管周C4d沉积的差异均有统计学意义.CTMR组肾间质CD4+和CD8+细胞数高于CAMR组和NOS组.CTMR组移植肾存活率为73.5％,NOS组为78.4％,CAMR组为41.7％；CAMR组预后最差(P＜0.05).结论 CAMR预示肾功能预后不良,CD4+和CD8+细胞浸润是CTMR较特异性的指标,可能有助于CTMR的诊断.     

肾移植术后抗体监测和移植肾病理学检查有助于早期诊断抗体介导的排斥反应

目的分析肾移植术后抗人类白细胞抗原(HLA)抗体监测和移植肾穿刺病理学检查早期诊断抗体介导的排斥反应(AMR)的必要性。方法筛选51例术后产生新生供体特异性抗体(dn DSA)的受者,检测供体特异性抗体(DSA)及其结合C1q的能力,同时进行移植肾穿刺病理诊断。对于符合AMR诊断的受者,比较分析移植肾功能不稳定组和稳定组受者的DSA类别、补体结合能力和移植肾病理组织Banff评分。对无排斥反应组、移植肾功能不稳定组和稳定组受者的移植物进行Kalan-Meier生存分析。结果在移植肾功能不稳定组和稳定组受者中,HLA抗体的不同类别、DSA的平均荧光强度(MFI)值、补体相关检测C1q结合力和C4d管周毛细血管沉积情况差异均无统计学意义(均为P0.05)。在组织形态学损伤方面,两组在微血管炎、动脉内膜炎、肾小管-间质炎、移植肾小球病、肾小管萎缩-间质纤维化等表现的Banff评分差异均无统计学意义(均为P0.05)。移植肾功能不稳定组受者移植物累积存活率显著低于稳定组,稳定组明显低于不符合排斥病理诊断的受者(P=0.002)。结论肾移植术后定期监测抗HLA抗体和做移植肾病理穿刺检查非常必要,有助于早期发现和诊断AMR。     

急性细胞性排斥伴补体裂解片断C4d沉积对移植肾预后的影响

目的探讨急性细胞性排斥伴肾小管周围毛细血管补体裂解片断(C4d)沉积对移植肾预后的影响。方法经病理证实的急性细胞性排斥肾移植患者145例,根据病理表现有否肾小管周围毛细血管C4d沉积,将其分为细胞性排斥+C4d阳性组(C4d阳性组)64例,单纯细胞性排斥组(C4d阴性组)81例。比较两组术前一般情况、排斥反应发病情况、抗排斥治疗、移植肾失功率及移植肾存活率。结果两组的术前一般情况比较差异无统计学意义(P0.05)。C4d阳性组的急性细胞性排斥反应发生时间明显早于C4d阴性组,比较差异有统计学意义(P0.05)。两组Banff分型Ⅰ型与Ⅱ型比例差异有统计学意义(P0.01)。随访期间C4d阳性组有22例(34%)移植肾失功,明显高于C4d阴性组的11例(14%),比较差异有统计学意义(P0.01)。Kaplan-Meier法分析发现C4d阳性组的移植肾存活率明显低于C4d阴性组(P0.01),移植肾的5年生存率分别为51%、79%。结论急性细胞性排斥反应伴肾小管周围毛细血管C4d沉积的肾移植患者,术后较早发生排斥反应,抗排斥治疗效果较差,移植肾存活率低。     

补体裂解片断C4d在移植肾急性排斥反应中的临床意义

目的探讨肾小管周围毛细血管补体裂解片断(C4d)沉积在移植肾急性排斥反应中的临床意义。方法对肾移植后发生急性排斥反应的78例受者进行移植肾活体穿刺检查,共获取移植肾活检穿刺标本86份。根据Banff97病理分型将86份活检标本分为BanffⅠ型32份,Ⅱ型51份,Ⅲ型3份。应用免疫组织化学法检测出86份标本中有30份出现肾小管周围毛细血管C4d沉积,阳性率为34.9%。分析C4d阳性其与Banff97分型、术前一般情况、抗排斥治疗、移植肾功能及移植肾预后的关系。结果BanffⅠ和Ⅱ型受者移植肾中C4d阳性率分别为21.9%和39.2%,两者相比差异无统计学意义(P=0.101)。有妊娠史、术前群体反应性抗体(PRA)>30%和再次移植的受者C4d阳性率较高。C4d阳性的受者发生排斥反应时血肌酐较阴性受者高,分别为(312.56±196.26)μmol/L和(210.97±136.59)μmol/L,两组差异有统计学意义(P=0.0115)。C4d阳性受者对激素和ATG冲击治疗与阴性受者比较,敏感率明显降低。C4d阳性的受者移植肾1年生存率较阴性受者低,分别为64.3%和90.0%,两组间差异有统计学意义(P=0.006)。结论移植肾C4d阳性的受者发生排斥反应时,对常规的激素冲击和ATG抗排斥治疗不敏感,血肌酐明显升高,移植肾1年存活率下降,受者预后较差。     

肾移植一年后急性排斥反应时移植肾组织中C4d表达阳性的临床研究

目的 观察肾移植1年后发生急性排斥反应时移植肾组织中补体片段C4d的表达情况,分析其对移植肾功能及预后的影响.方法 选择肾移植时间超过1年,临床诊断为急性排斥反应并经病理穿刺活检证实的肾移植受者36例为研究对象.以第1例受者移植肾组织穿刺时间为观察起点(2006年3月),以此项研究结束时间为观察终点(2010年4月).应用C4d多克隆抗体对移植肾穿刺组织行免疫组织化学染色,检测C4d在移植肾组织中的表达情况;根据检测结果,分为C4d阳性组和阴性组,分析和比较两组在观察时间段内移植肾功能的变化及存活时间.结果 在36例受者的移植肾穿刺标本中,C4d阳性16例(44.4%),C4d阴性20例(55.6%);C4d阳性组和阴性组移植肾组织中嗜酸性粒细胞浸润数量分别为(9.4±4.5)个和(2.6±1.8)个,两组比较,差异有统计学意义(P＜0.05).在观察时间段内,所有受者血清肌酐均有不同程度上升,但C4d阳性组上升幅度与C4d阴性组比较,差异无统计学意义(P＞0.05);C4d阳性组和C4d阴性组受者移植肾功能丧失率分别为31.3%(5/16)和30.0%(6/20),两组比较,差异无统计学意义(P＞0.05).C4d阳性组和C4d阴性组受者移植肾穿刺后的巾位存活时间分别为(19.3±5.3)个月和(22.5±7.4)个月,两组比较,差异无统计学意义(P＞0.05).结论 肾移植1年后发生急性排斥反应时,移植肾组织中C4d表达阳性对其功能及存活时间无明显影响.     

移植肾抗体介导排异中C4d的病理机制及临床意义

移植肾排斥反应中的抗体介导机制已得到了明确分类,而C4d在肾小管周毛细血管(PIC)中的沉积是其特征性表现,与肾功能及移植肾预后亦有紧密联系.本文对C4d在移植肾抗体介导排斥反应中的病理作用及指导治疗的意义进行综述.     

移植肾组织中补体C4d沉积在CAN的诊断和治疗中的临床意义

目的 探讨移植肾组织中补体C4d沉积在慢性移植肾肾病(CAN)的诊断和治疗中的临床意义.方法 将2000年1月至2008年8月间诊断为CAN,且已行移植肾活检,并能收集到活检后2年以上随访资料者纳入研究.符合标准者共有86例,其中男性53例,女性33例,移植时年龄18～65岁.应用免疫组织化学染色方法检测移植肾组织活检标本C4d的表达.所有患者在行移植肾穿刺诊断为CAN后均给予了常规治疗.结果 86例患者中,C4d沉积阳性者(C4d阳性组)39例,C4d沉积阴性者(C4d阴性组)47例,两组患者在性别、年龄、供肾来源、多次移植、移植时群体反应性抗体水平等各指标的比较,差异均无统计学意义(P＞0.05).活检2年后,C4d阳性组和阴性组患者的SCr水平分别为(551.5±140.4)和(443.0±133.1)μmol/L,两组比较,差异有统计学意义(P＜0.05);并且C4d阳性组患者移植肾功能丧失率(23.1%,10/39)也显著高于C4d阴性组(8.5%,4/47),两组比较,差异有统计学意义(P＜0.05).CAN治疗前,C4d阳性组发生高血压和高血脂者多于阴性组(P＜0.05);常规治疗后,剔除移植肾功能丧失者,两组间发生高血压、高血脂、高血糖和高血尿酸者差异无统计学意义(P＞0.05).结论 C4d阳性的CAN患者提示有慢性体液排斥反应的参与,临床常规治疗预后较差,若针对体液免疫反应进行干预,能够改善移植肾长期存活.     

丙型肝炎病毒感染对肾移植受者排斥反应及人/肾存活率的影响

目的 研究丙型肝炎病毒(HCV)感染是否影响移植肾急性和慢性排斥反应的发生率,以及受者和移植肾的存活率.方法 对1992年6月至2004年6月所行肾移植的495例受者进行了随访,其中术前HCV抗体阳性受者27例(HCV阳性组),随机抽取HCV抗体阴性受者27例作为对照组,行组间配对研究,分析HCV感染状态对肾移植受者急性和慢性排斥反应发生率以及人/肾存活率的影响.结果 HCV阳性组受者急性排斥反应的发生率显著高于对照组(19.14%和6.38%,P<0.01),HCV阳性组慢性排斥反应的发生率也明显高于对照组(23.40%和12.76%,P<0.01),对照组肾移植后1、3、5年人/肾存活率显著高于HCV阳性组,差异有统计学意义(P<0.01).结论 HCV感染可以明显增加肾移植受者急性和慢性排斥反应的发生率,降低人/肾存活率.     

肾移植术后血清抗MICA抗体与慢性排斥反应的相关性

目的 探讨肾移植受者的抗MICA抗体水平与慢性排斥反应的相关性及其对移植肾功能的影响.方法 共有105例受者被作为研究对象纳入分析,其中发生慢性排斥反应者(慢排组)43例,移植肾功能正常者(对照组)62例.记录两组受者术前群体反应性抗体(PRA)、HLA抗原错配数、供肾冷缺血时间、出院时血清肌酐(SCr)水平、术后免疫抑制方案以及入组时间(入组时距肾移植手术时间)等资料,并进行比较.受者分组后,抽取受者外周血,检测SCr及抗MICA抗体水平,抗MICA抗体的检测采用Luminex 100免疫磁珠流式细胞仪技术.观察与比较抗MICA抗体阳性受者和抗MICA抗体阴性受者间术后3个月内发生急性排斥反应(AR)的次数和移植肾功能的差异.移植肾功能的评价采用血清肌酐变化率(△SCr/M),即(入组时SCr值-出院时SCr值)/入组时间.结果 两组受者在性别、年龄、HLA抗原错配数、供肾冷缺血时间、术后免疫抑制方案、出院时SCr水平及入组时间的比较,差异均无统计学意义(P＞0.05).分组后,慢排组受者SCr水平和抗MICA抗体阳性受者比例均明显高于对照组,两组比较,差别均有统计学意义(P＜0.01,表1).抗MICA抗体阳性受者术后3个月内发生的AR次数明显多于抗MICA抗体阴性受者,二者比较,差异有统计学意义(P＜0.05).抗MICA抗体阳性受者的△SCr/M为8.3±3.6,明显高于抗MICA抗体阴性受者的2.4±2.6,二者比较,差异有统计学意义(P＜0.05).结论 抗MICA抗体的表达与慢性排斥反应的发生相关,移植前进行MICA配型可减少术后移植肾慢性排斥反应的发生,有助于延长移植肾的长期存活.     

C4d和供者特异性抗体检测在肾移植抗体介导排斥反应中的应用研究进展

抗体介导排斥反应(AMR)已经成为导致移植物丢失的主要原因。C4d在管周毛细血管(PTC)部位沉积是肾移植体液免疫活跃的标志,单纯C4d阳性不能确诊为AMR,当临床上出现循环供者特异性抗体(DSA)、病理特征和/或移植肾功能不全时必须考虑AMR。C4d和DSA检测阳性与移植物存活率下降密切相关,特别是在检测时就出现移植物功能不全者。本文主要围绕C4d和DSA检测在肾移植AMR中的应用研究作一综述。     

Clinicopathological and prognostic analysis of children with primary IgA nephropathy with C1q deposition

Objective To investigate the clinical and pathological features and prognosis of children with IgA nephropathy with C1q deposition. Methods The children with IgA nephropathy diagnosed by renal biopsy from January 1, 2000 to December 30, 2017 were retrospectively analyzed and divided into C1q deposit group and C1q negative group according to glomerular immunofluorescence examination. Follow-up until the patient's serum creatinine doubled, glomerular filtration rate decreased by more than 50%, entering end-stage kidney disease, renal replacement therapy or death. Kaplan-Meier survival analysis was used to evaluate the renal survival rate in two groups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the effect of C1q deposition on the prognosis of patients with IgA nephropathy. Results There were 60 cases in C1q deposition group and 60 cases in C1q negative group. (1) the initial eGFR and plasma albumin in C1q deposition group were lower than those in C1q negative group, while the levels of serum creatinine, serum cholesterol and 24 hour urinary protein in C1q group were higher than those in C1q negative group (all P＜0.05). (2) pathological indexes: Mesangial cell proliferation, tubular atrophy/interstitial fibrosis, and cell/fibrocytic crescein score in C1q negative group were significantly higher than those in C1q negative group (all P＜0.0.5). (3) Kaplan-Meier analysis showed that there was significant difference in renal cumulative survival rate between the two groups (Log-rank test: χ2=6.801, P=0.009). Cox proportional hazard regression model showed that the risk of renal end-point events in IgAN children with C1q deposition group was 5.772 times higher than that in C1q negative group (HR=5.772, 95%CI: 1.353-24.6211, P=0.018). Conclusion C1q deposition is an independent risk factor for the progress of renal function in IgA nephropathy children.     

Monocytes and peritubular capillary C4d deposition in acute renal allograft rejection

BACKGROUND: Peritubular capillary (PTC) deposition of complement split factor C4d in renal allografts has been shown to be closely associated with circulating antidonor antibodies and a marker for relatively poor graft survival. Monocyte/macrophage (MO) infiltration of renal allografts has been shown to adversely affect graft survival. The purpose of this study was to assess whether the two phenomena are related. METHODS: Twenty-three biopsies (from 15 patients) demonstrated diffuse strong staining of PTC for C4d (C4d+ group) and acute tubular injury with or without significant cellular rejection, while 28 biopsies (with acute rejection) but negative for PTC C4d served as controls (C4d- group). RESULTS: The C4d+ group demonstrated significantly greater glomerular and interstitial MO infiltration than did the C4d- group [3.4 +/- 2.0 vs. 0.2 +/- 0.3 MO/glomerulus, P < 0.0001; 12.9 +/- 9.2 vs. 6.5 +/- 5.0 MO/high power field (hpf), P = 0.0030]. Neutrophilic (PMN) infiltration of glomeruli and PTC was also significantly greater in the C4d+ group than in the C4d- one (0.8 +/- 0.6 vs. 0.3 +/- 0.3 PMN/glomerulus, P = 0.0003; 0.9 +/- 0.8 vs. 0.4 +/- 0.3 PTC PMN/hpf, P = 0.0035). CONCLUSION: The results indicate a close association between PTC C4d deposition and MO infiltration, particularly glomerular, and confirm previous observations regarding the correlation of PTC C4d staining and PMN infiltration.     

Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: a contribution of humoral immunity to chronic allograft rejection

Endothelial deposition of the complement split product C4d is an established marker of antibody-mediated acute renal allograft rejection. A contribution of alloantibody-dependent immune reactions to chronic rejection is under discussion. In this study, the association of immunohistochemically detected endothelial C4d deposition in peritubular capillaries (PTC) with morphologic features of chronic renal allograft injury was investigated in a large study cohort. C4d deposits in PTC were detected in 73 (34%) of 213 late allograft biopsies performed in 213 patients more than 12 mo after transplantation (median, 4.9 yr) because of chronic allograft dysfunction. Endothelial C4d deposition was found to be associated with chronic transplant glomerulopathy (CG) (P < 0.0001), with basement membrane multilayering in PTC (P = 0.01), and with an accumulation of mononuclear inflammatory cells in PTC (P < 0,001). Furthermore, C4d deposits in PTC (in biopsies with normal glomerular morphology) were associated with development of CG in follow-up biopsies. Other morphologic features of chronic allograft nephropathy (with exception of tubular atrophy) were not associated with C4d deposits in PTC. Analyses of previous and follow-up biopsies revealed that C4d deposits may occur de novo and may also disappear at any time after transplantation. In conclusion, the data suggest that complement activation in renal microvasculature, indicating humoral alloreactivity, contributes to chronic rejection characterized by chronic transplant glomerulopathy and basement membrane multilayering in PTC.     

补体旁路途径过度活化在恶性高血压肾硬化中的作用

目的研究补体旁路途径(alternative complement pathway)过度活化在恶性高血压肾硬化中的作用。方法(1)选取本院经肾穿刺活检证实为恶性高血压肾硬化患者50例为病例组,零点行肾穿刺活检的供肾者25例为正常对照组,采用酶联免疫吸附法(ELISA)检测血浆及尿液中的补体旁路途径活化起始B因子、正向调节P因子、负向调节H因子及补体活化终末产物C3a、C5a水平。(2)免疫组化法检测补体活化终末产物C5b-9、C4d及凝集素途径活化产物甘露糖结合凝集素(MBL)在肾活检组织的沉积;免疫荧光双染检测C5b-9与CD34(内皮细胞标志物)在小动脉内皮及肾小球毛细血管内皮的沉积。结果(1)恶性高血压肾硬化患者血浆及尿液中补体B因子、P因子、C3a及C5a均高于正常对照组(均P<0.05),而H因子则低于正常对照组(P<0.05)。(2)恶性高血压肾硬化患者血浆中补体P因子与24 h尿蛋白量呈正相关(rs=0.465,P=0.001),而补体B因子、H因子、C3a、C5a与血肌酐及24 h尿蛋白量无明显相关性。恶性高血压肾硬化患者尿B因子/尿肌酐、尿P因子/尿肌酐、尿C3a/尿肌酐与血肌酐均呈正相关(rs=0.483,P<0.001;rs=0.352,P=0.012;rs=0.319,P=0.024),尿H因子/尿肌酐与血肌酐及24 h尿蛋白量均呈负相关(rs=-0.299,P=0.035;rs=-0.342,P=0.015),尿C5a/尿肌酐与血肌酐及24 h尿蛋白量均呈正相关(rs=0.525,P<0.001;rs=0.496,P<0.001)。(3)免疫组化显示,恶性高血压肾硬化患者C5b-9沉积于小动脉壁及肾小球毛细血管壁,而正常对照组肾组织中未见沉积。恶性高血压肾硬化患者肾脏C5b-9沉积强度评分与血肌酐及24 h尿蛋白量呈正相关(rs=0.791,P<0.001;rs=0.345,P=0.014)。双重免疫荧光标记法可见C5b-9、CD34沉积于小动脉内皮及肾小球毛细血管内皮。(4)恶性高血压肾硬化患者血浆中B因子与C3a(r=0.331,P=0.022)、P因子与C5b-9评分(rs=0.300,P=0.034)均呈正相关;尿液中补体旁路途径活化B因子与C3a、C5a及C5b-9均呈正相关(rs=0.311,P=0.028;rs=0.465,P=0.001;rs=0.428,P=0.002),P因子与C3a、C5a也均呈正相关(rs=0.307,P=0.030;rs=0.442,P=0.001)。恶性高血压肾硬化患者免疫组化可见C4d沉积于小动脉及肾小球,而未见凝集素途径活化产物MBL沉积。结论补体旁路途径过度活化可能参与恶性高血压肾硬化的发生。恶性高血压肾硬化严重程度与补体旁路途径的活化水平相关。     

Focal C4d+ in Renal Allografts Is Associated with the Presence of Donor-Specific Antibodies and Decreased Allograft Survival

Diffuse peritubular capillary C4d deposition in renal allograft biopsies is associated with donor-specific antibodies (DSA) and graft failure. The significance of focal C4d+ is unclear. We reviewed 368 biopsies from 301 patients performed for renal dysfunction or proteinuria over 5 years. Diffuse C4d+, focal C4d+ and C4d- detected by immunofluorescence occurred in 9.5%, 20.9% and 69.4% of biopsies, respectively. Patients were similar in gender, age, cause of renal disease, donor source, HLA mismatch, serum creatinine at baseline and interval from transplantation to biopsy. Diffuse and focal C4d+ were associated with acute cellular rejection (p < 0.001). Transplant glomerulopathy was associated with diffuse C4d+. DSA at the time of biopsy, were positive in 79.3% of diffusely C4d+ patients, 68.8% of those with focal C4d+ (p = 0.27) and 9.9% of patients with C4d- (p < 0.001, compared to either the focal or diffuse groups, respectively). Allograft survival at 40 months was lower in diffuse C4d+ compared to the C4d- group (p = 0.014), but not when compared to the focal C4d+ group. There was a clear trend toward worse graft survival in patients with focal C4d+ in this time interval, but focal C4d+ compared to both diffuse C4d+ and C4d-groups was not statistically significant (p = 0.08).     

Analysis of the clinical pathological characteristics and prognosis of primary IgA nephropathy with hypertension

Objective To investigate the clinic-pathological features and prognostic risk factors of IgA nephropathy (IgAN) with hypertension (HTN). Methods Primary IgAN patients diagnosed with biopsy from January 2016 to December 2017 were recruited. Patients were divided into IgAN with normal blood pressure (IgAN-NTN) group and IgAN with hypertension (IgAN-HTN) group based on the pressure value when performing the kidney biopsy. The clinical and pathological data were collected and compared between the two groups. Kaplan-Meier method was conducted for renal results, whereas the Cox regression model was exploited to analyze the prognostic factors in the progression of IgAN-HTN patients. Results The total number of enrolled patients was 275 cases, 170 (61.82%) of which had normal pressure and 105 individuals (38.18%) resulted in hypertension. The IgAN-HTN group in terms of male proportion, age, systolic pressure, diastolic pressure, serum urea nitrogen, serum creatinine, serum uric acid, 24 h urinary protein, triacylglycerol, complement C4 and so on were higher than those in the IgAN-NTN group (all P＜0.05). The incidence of gross hematuria and the level of estimated glomerular filtration rate (eGFR) were significantly lower than those in the NTN group (all P＜0.001). For the aspect of light microscope pathological manifestations, IgAN-HTN group exhibited more severe histological lesions including glomerular sclerosis, renal tubular atrophy or renal interstitial fibrosis, interstitial vascular injury than IgAN-NTN group (all P＜0.05). Immunofluorescence examination results showed that the deposition ratio of C1q in IgAN-HTN group was higher than that in IgAN-NTN group (P=0.015). By employing Kaplan-Meier method, the cumulative renal survival rate in the HTN group was much lower than that in the NTN group (Log-rank test: χ2=6.456, P=0.011). For the patients in IgAN-HTN group, the cumulative renal survival rate in the dyslipidemia group was much lower than that in the ortholiposis group (Log-rank test: χ2=5.093, P=0.024). There was no significant difference in the cumulative renal survival rate between the blood pressure control group and the unqualified group (Log-rank test: χ2=1.036, P=0.309). As a result of univariate and multivariable Cox regression analysis, total cholesterol, eGFR and 24 h urinary protein were risk factors for renal progression of IgAN patients with hypertension. Conclusions The clinical manifestations and renal pathological changes in patients with IgAN-HTN are more serious than those in IgAN-NTN patients, which result in worse prognosis. IgAN-HTN patients should be paid more attention to the management of serum lipid level during treatment and follow-up.     

Clinico-pathological features and renal outcomes of primary IgA nephropathy with IgM deposition

Objective To investigate the clinico-pathological features and renal outcomes of primary IgA nephropathy (IgAN) with glomerular IgM deposition. Methods Primary IgAN diagnosed with biopsy from January 2006 to December 2011 were recruited. Patients were divided into groups according to IgM deposition (Group A) and without IgM deposition (Group B). In addition, Group A was subdivided into two groups based on the position of IgM deposits as the mesangium (Group A1) and both mesangium and capillary wall (Group A2). Renal outcomes were defined as end stage renal disease (ESRD) and/or the doubling of baseline serum creatinine. Clinico-pathological features were retrospectively compared. Kaplan-Meier was conducted for renal outcomes, and Cox regression model was used to analyze the prognostic value of IgM deposition and the position of IgM deposition in the progression of nephropathy in IgAN patients. Results 939 patients were enrolled with 422 (44.9%) having IgM deposition (Group A). Of the 422 patients, 382 patients were divided as Group A1, whereas 40 patients were noted as Group A2. Compared to Group B, hemoglobin, serum protein, albumin and serum IgG levels in group A were significantly lower, and the cholesterol and serum IgM levels were significantly higher (all P＜0.05). There was no significant difference in serum creatinine, estimated glomerular filtration rate (eGFR), urinary protein, blood pressure and uric acid between group A and B. In terms of pathological manifestations, patients in Group A exhibited more severe histological lesions including glomerular sclerosis, S1, M1 and interstitial inflammatory cell infiltration (all P＜0.05). Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A was significantly higher than that in group B (all P＜0.05). By Kaplan-Meier, cumulative renal survival rate has no significant difference between Group A and B (Log-rank test χ2=0.019, P=0.891). Univariate and multivariable Cox regression analysis showed that IgM deposition had no significant effect on the renal progression in IgAN patients. Subgroup analysis showed that patients in Group A2 exhibited higher urine protein, creatinine and blood pressure, and lower eGFR and serum albumin, also had worse histological lesions including M1, E1 and T1-2 of Oxford classification (all P＜0.05), Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A2 was significantly higher than that in group A1 (all P＜0.05). By Kaplan-Meier, renal survival rates calculated from outcomes were lower in Group A2 (Log-rank test χ2=18.207, P＜0.001). In addition, IgM deposited both in the mesangium and capillary wall was a risk factor for renal progression of IgAN patients with IgM deposition by a univariate Cox hazards regression mode and multivariable-adjusted Cox models (HR=3.621, 95%CI 1.924-6.814, P＜0.001; HR=2.309, 95%CI 1.176-4.533, P=0.015 respectively). Conclusions The IgAN patients with IgM deposition relatively had more severe clinico-pathological changes, especially those with IgM deposited both in the mesangium and capillary wall. In this study, IgM deposition was not found to be an independent risk factor for the prognosis of kidney in IgAN patients. However, IgM deposited both in the mesangium and capillary wall was an independent risk factor for renal prognosis in IgAN patients with IgM deposition.     

移植肾小球炎的细胞类型及其与管周毛细血管C4d沉积的关系

目的 研究同种异体肾移植术后急性排斥患者肾小球炎的细胞类型及其与管周毛细血管（PTC）C4d沉积的关系。 方法 2006年6月至2009年6月在本中心行同种异体肾移植手术后,肾功能异常且病理证实为急性排斥并发小球炎受者51例的肾活检组织为研究对象。免疫组化方法检测同一活检标本连续切片内T细胞表面标记物CD3、巨噬细胞表面标记物CD68、体液性排斥特异性标记物C4d、细胞毒T淋巴细胞标记物颗粒酶B及调节性T淋巴细胞标记物Foxp3的表达情况。根据PTC有无C4d沉积将受者分为C4d阳性组和C4d阴性组,定量计数小球内阳性细胞数,并计算每个小球的平均细胞数。 结果 C4d阳性与C4d阴性的急性排斥受者小球内浸润的炎细胞数分别为17.79±7.70和8.17±3.80,差异有统计学意义（P < 0.01）。C4d阳性急性排斥受者小球内以巨噬细胞浸润为主,与C4d阴性者差异有统计学意义（13.73±7.03 比2.57±1.22,P < 0.01）。C4d阴性急性排斥受者小球内以T淋巴细胞为主,与C4d阳性者差异有统计学意义（5.60±2.81比4.05±2.60,P = 0.023）。C4d阴性与C4d阳性急性排斥受者小球内T淋巴细胞都以细胞毒细胞为主 （3.37±2.34比4.27±2.41,P = 0.141）,而没有调节性T淋巴细胞的浸润。 结论 肾移植术后急性排斥患者小球内炎细胞浸润总数与PTC的C4d沉积有关。C4d阳性患者小球炎细胞数多于C4d阴性患者。C4d阳性患者小球炎细胞以巨噬细胞浸润为主;C4d阴性患者小球炎细胞以T淋巴细胞浸润为主。两组患者小球内T淋巴细胞都以细胞毒细胞为主。