C4d沉积在抗体介导的慢性排斥反应中的临床意义

目的 探讨移植肾肾小管周围毛细血管补体片段C4d沉积与抗体介导的慢性排斥反应的病理形态、移植肾功能及预后的关系.方法 应用免疫组织化学技术检测77例肾移植受者移植肾肾小管周围毛细血管中C4d的沉积情况,根据检测结果分为C4d阳性组(35例)和C4d阴性组(42例).检测并比较C4d阳性和阴性组受者移植肾的病理形态结构、移植肾功能及预后.结果 与C4d阴性组比较,C4d阳性组受者移植肾肾小管萎缩和肾小球基底膜增生分层的例数明显增多,差异有统计学意义(P＜0.05).C4d阳性组受者的血肌酐水平在移植肾穿刺后12个月时较C4d阴性组受者明显升高,分别为(379.1±260.2)μmol/L和(260.5±175.3)μmol/L,差异有统计学意义(P＜0.05).C4d阳性组受者移植肾穿刺明确C4d阳性后1年内移植肾存活率为62.9%(22/35),而阴性组受者为83.3%(35/42),两组比较,差异有统计学意义(P＜0.05).结论 在抗体介导的慢性排斥反应中,移植肾C4d沉积常见的病理学改变为肾小管萎缩和肾小球基底膜增生分层,C4d阳性抗体介导的体液性慢性排斥反应加快了移植肾功能丧失的进展速度,使C4d阳性受者的移植肾功能丧失率升高,导致存活率降低.     

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.     

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.     

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。     

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.     

急性体液性排斥反应对移植肾预后的影响

目的 探讨急性体液性排斥反应对移植肾预后的影响.方法 共有1098例接受首次尸体肾移植的受者纳入研究.所有受者术后均采用以他克莫司或环孢素A为基础的三联免疫抑制方案,当发生排斥反应时,采用甲泼尼龙冲击治疗,疗效较差者则联合应用莫罗单抗-CD3或丙种球蛋白或行血浆置换进行治疗.术后1年内经病理检查证实,有53例受者发生急性体液性排斥反应(急性体液性排斥反应组),109例发生急性细胞性排斥反应(急性细胞性排斥反应组),其余936例受者术后1年内肾功能稳定(对照组).分析和比较3组受者性别、年龄、术前淋巴毒、HLA抗原错配数、群体反应性抗体(PRA)水平及供肾冷/热缺血时间等冈素间的差异,比较3组受者术后移植肾功能丧失情况及移植肾存活率,分析完全逆转的急性体液性排斥反应与细胞性排斥反应对移植肾预后的影响.结果 3组受者在性别、年龄、术前淋巴细胞毒性试验、供肾冷缺血时间及术后随访时间等方面比较,差异均无统计学意义(P＜0.05).急性体液性排斥反应组和急性细胞性排斥反应组受者在术前HLA抗原错配数、PRA水平及供肾热缺血时间等方面均明显高于对照组,与对照组比较,差异均有统计学意义(P＜0.05).随访期间,急性体液性排斥反应组受者移植肾功能丧失的发生率为27.4%(14/53),明显高于急性细胞性排斥反应组的7.3%(8/109)和对照组的2.2%(21/936),3组间差异均有统计学意义(P＜0.01).通过kaplan-meier生存分析发现,急性体液性排斥反应组受者的移植肾存活率明显低于急性细胞性排斥反应组和对照组(P＜0.01).剔除发生排斥反应后未逆转者,3组间移植肾存活率的比较,差异均无统计学意义(P＞0.05).结论 急性体液性排斥反应明显影响移植肾存活,但完全逆转的急性体液排斥反应并不影响移植肾的预后.     

免疫吸附联合他克莫司和霉酚酸酯逆转肾移植后急性体液性排斥反应

目的探讨免疫吸附(IA)联合他克莫司(FK506)和霉酚酸酯(MMF)治疗C4d阳性的急性体液性排斥反应(AHR)的临床效果。方法1999年4月至2003年6月间行同种异体尸肾移植490例,其中9例受者发生AHR,其诊断均依据Banff 97标准,Banff分级为Ⅱ级5例,Ⅲ级4例。患者发生AHR后均采用免疫吸附联合FK506 MMF 激素治疗,同时辅以连续性血液净化。治疗前、后行移植肾活检,分别进行病理观察、免疫荧光和免疫组织化学检测,同时检测患者血清HLA、免疫球蛋白水平以及肝、肾功能。结果治疗后,9例AHR患者中有8例得到逆转;1例治疗无效,转而采用血液透析治疗。患者的HLA-Ⅰ、Ⅱ水平较治疗前明显下降,分别为(5.9±2.9)%和(2.2±0.6)%;血清总的免疫球蛋白水平也明显降低;患者移植肾肾小管周围毛细血管C4d沉积强度较治疗前明显减轻,其中5例患者C4d转阴;肾小球浸润细胞明显减少,肾小管炎症减轻,间质浸润细胞减少,血管炎减轻。患者在接受免疫吸附治疗过程中均未出现严重并发症。结论免疫吸附联合FK506 MMF可有效地逆转C4d阳性的急性体液性排斥反应。     

肾移植术后中远期急性排斥反应临床研究

目的探讨肾移植术后中远期移植肾急性排斥反应(AR)发生影响因素及移植肾生存情况。 方法回顾性分析浙江大学医学院附属第一医院肾脏病中心2018年1月至2019年12月因血清肌酐水平升高而接受移植肾病理活检并确诊移植肾AR受者临床资料,共纳入43例受者,其中急性抗体排斥反应组17例,急性T细胞排斥反应组26例;同时纳入同期(2周内)肾移植且移植肾功能正常的39例受者为对照组。正态分布计量资料比较采用配对t检验或单因素方差分析。计数资料比较采用χ²检验或Fisher确切概率法。采用Kaplan-Meier进行生存分析,并采用log-rank进行比较。P<0.05为差异有统计学意义。 结果急性抗体排斥反应组HLA-A错配2个比例(4/17)高于对照组(1/39),差异有统计学意义(P＝0.026)。急性抗体排斥反应组和急性T细胞排斥反应组AR发生时和末次血清肌酐和估算肾小球滤过率(eGFR)均高于AR发生前(P均<0.05);急性抗体排斥反应组和急性T细胞排斥反应组AR发生时和末次血清肌酐和eGFR均高于对照组(P均<0.05);急性抗体排斥反应组进入慢性肾脏病(CKD)-4期受者比例低于急性T细胞排斥反应组(χ²＝5.73,P<0.05);急性T细胞排斥反应组进入CKD-4期受者比例以及急性抗体排斥反应组移植肾失功比例均高于对照组(χ²＝17.727和9.882,P均<0.05)。AR发生时急性抗体排斥反应组和急性T细胞排斥反应组受者均接受PRA检测,前者PRA-Ⅰ和PRA-Ⅱ阳性比例分别为41.2%(7/17)和88.2%(15/17),均高于后者[11.5%(3/26)和26.9%(7/26)],差异均有统计学意义(P＝0.042,P<0.001)。急性抗体排斥反应组、急性T细胞排斥反应组及对照组术后分别有13、24和38例受者应用他克莫司。发生AR时,急性抗体排斥反应组他克莫司血药浓度[(3.72±0.76)ng/mL]与急性T细胞排斥反应组[(3.37±0.86)ng/mL]均低于对照组[(5.73±1.25)ng/mL],差异均有统计学意义(P均<0.05);急性抗体排斥反应组与急性T细胞排斥反应组他克莫司血药浓度均低于发生AR前[(6.27±1.18)和(6.33±1.63)ng/mL],差异均有统计学意义(t＝7.120和6.216,P均<0.05)。急性抗体排斥反应组4例受者应用以环孢素为基础的免疫抑制方案,其中3例术后33、36和55个月环孢素血浓度分别为112.4、138.3和7.0 ng/mL,均低于要求血药浓度。急性T细胞排斥反应组2例应用环孢素受者术后16和177个月环孢素血药浓度分别为43.2和24.6 ng/mL,均低于要求血药浓度。随访至2021年6月30日,急性抗体排斥反应组移植肾生存率低于对照组(χ²＝8.738,P<0.05)。 结论HLA-A位点错配及他克莫司低血药浓度是肾移植术后中远期诱发AR的重要原因。急性抗体介导排斥反应是移植肾生存重要影响因素。     

黄嘌呤氧化脱氢酶在大鼠肾移植急性排斥反应中的作用

目的 观察黄嘌呤氧化脱氢酶(XOD)在大鼠肾移植急性排斥反应中的作用.方法 实验分同系移植组和异系移植组两组.采用左肾原位移植术建立大鼠.肾移植模型.分别于术后1、4、7 d切取受体左肾,观察其形态学改变,应用比色法检测移植肾组织中XOD和活性氧(ROS)的活力,应用免疫组织化学技术检测XOD的表达.结果 异系移植组术后第4、7天呈现典型的急性排斥反应的病理改变.该组各时间点的XOD活力、ROS水平、Banff总分及免疫组织化学评分与同系移植组比较,差异均有统计学意义(P＜0.05).异系移植组移植肾XOD活力、ROS水平、Banff总分及免疫组织化学评分之间均呈正相关(r≥0.751,P＜0.01).XOD表达于肾小管上皮细胞、肾小球内皮细胞和浸润的单核巨噬细胞中.结论 XOD与肾移植急性排斥反应的发生发展密切相关.     

Role of CXCR3 in cellular but not humoral renal allograft rejection

CXCR3, a chemokine receptor mainly expressed by T cells, is involved in animal transplant models and in human allograft rejection. CXCR3 expression was localized in formalin-fixed, paraffin-embedded renal allograft biopsies without signs of rejection (C4d-negative, Banff 0, n = 16), with C4d deposits as a sign of humoral rejection (C4d-positive, Banff 0, n = 8), with cellular rejection (C4d-negative, Banff I, n = 7) and with signs of both cellular and humoral rejection (C4d-positive, Banff 1, n = 5). Small, round infiltrating cells were CXCR3-positive. A high number of these cells was present in biopsies with cellular rejection (independent of C4d deposition). CXCR3-positive cells diffusely infiltrated the interstitium, including the tubular epithelium (tubulitis). CXCR3 scores and the area of CXCR3 staining were significantly higher in cellular rejection, when compared to biopsies without rejection, and with deposition of C4d alone. CXCR3-positive cells infiltrate renal allografts during cellular rejection, whereas C4d deposition is not associated with the recruitment of these cells.     

C4d deposition in acute rejection: an independent long-term prognostic factor.

Peritubular capillary deposition of C4d has been demonstrated to be associated with both acute humoral and vascular rejection and increased graft loss. Whether it is an independent predictor of long-term graft survival rates is uncertain. The biopsies (n = 126) from all patients (n = 93) with a tissue diagnosis of acute rejection that were performed between July 1, 1995, and December 31, 1997, were classified according to Cooperative Clinical Trials in Transplantation (CCTT) criteria. Fresh frozen tissue was immunostained for C4d. There were 58 patients with CCTT type I (interstitial) rejection and 35 with CCTT type II (vascular) rejection. For 34 patients, at least one biopsy exhibited peritubular C4d deposition (C4d+ group). The C4d+ group had proportionately more female patients (P = 0.003), more patients with high (>30%) panel-reactive antibody levels (P = 0.024), more patients with resistance to conventional antirejection therapy (P = 0.010), and fewer patients with postrejection hypertension (P = 0.021) and exhibited a greater rate of graft loss (38 versus 7%, P = 0.001). Peritubular C4d deposition was associated with significantly lower graft survival rates in the CCTT type I rejection group (P = 0.003) and the CCTT type II rejection group (P = 0.003). Multivariate analyses demonstrated that peritubular C4d deposition (P = 0.0002), donor age (P = 0.0002), cold ischemic time (P = 0.0211), and HLA matches (P = 0.0460) were significant independent determinants of graft survival rates. Peritubular C4d deposition is a significant predictor of graft survival rates and is independent of histologic rejection type and a variety of clinical prognostic factors.     

Four Stages and Lack of Stable Accommodation in Chronic Alloantibody-Mediated Renal Allograft Rejection in Cynomolgus Monkeys

The etiology of immunologically mediated chronic renal allograft failure is unclear. One cause is thought to be alloantibodies. Previously in Cynomolgus monkeys, we observed a relationship among donor-specific alloantibodies (DSA), C4d staining, allograft glomerulopathy, allograft arteriopathy and progressive renal failure. To define the natural history of chronic antibody-mediated rejection and its effect on renal allograft survival, we now extend this report to include 417 specimens from 143 Cynomolgus monkeys with renal allografts. A subset of animals with long-term renal allografts made DSA (48%), were C4d positive (29%), developed transplant glomerulopathy (TG) (22%) and chronic allograft arteriopathy (CAA) (19%). These four features were highly correlated and associated with statistically significant shortened allograft survival. Acute cellular rejection, either Banff type 1 or 2, did not correlate with alloantibodies, C4d deposition or TG. However, endarteritis (Banff type 2) correlated with later CAA. Sequential analysis identified four progressive stages of chronic antibody-mediated rejection: (1) DSA, (2) deposition of C4d, (3) TG and (4) rising creatinine/renal failure. These new findings provide strong evidence that chronic antibody-mediated rejection develops without enduring stable accommodation, progresses through four defined clinical pathological stages and shortens renal allograft survival.     

移植肾组织中C4d沉积、浆细胞聚集性浸润及其与体液性排斥反应的关系

目的 检测因排斥反应而丧失功能的移植肾组织中浆细胞的浸润情况及补体CA裂解产物C4d的沉积情况,分析浆细胞浸润、C4d沉积与体液性排斥反应的相关性.方法 切取40例因排斥反应而丧失功能的移植肾,取其组织,进行HE染色和免疫组织化学染色,依据Banff 97标准对排斥反应进行病理分型,检测肾组织中C4d、CD38和CD138的表达,分析三者之间的相关性.同时以10例非排斥因素导致移植肾功能丧失者为对照.结果 40例排斥反应中,超急性排斥反应5例,急性排斥反应9例,慢性排斥反应26例;40例中,C4d阳性17例(42.5%),CD38阳性25例(62.5%),CD138阳性23例(57.5%);有9例(22.5%)的C4d、CD38和CD138同时阳性,其中超急性排斥反应1例,急性排斥反应3例,慢性排斥反应5例.经Spearman等级相关分析,C4d的沉积与CD38和CD138的表达存在相关性(P＜0.05,P＜0.01).10例对照者中,C4d和CD38染色阳性各1例,无C4d、CD38和CD138均阳性的病例.结论 CD38和CD138与C4d的沉积存在相关性,提示移植肾中聚集性浸润的浆细胞可能通过局部分泌抗体的方式参与移植肾的体液排斥机制.     

Tregs对同种异体牙移植免疫排斥反应的抑制作用

目的 探讨Tregs对同种异体牙移植术后免疫排斥反应的抑制作用,提供一种免疫移植方法.方法 免疫抑制剂Tregs给予白鼠尾巴静脉注射1周,建立白鼠同种异体牙移植模型,术后观察移植牙存活、排异发生率及程度.结果同种异体牙均诱发免疫排斥反应,但Tregs注射后免疫排斥反应的时间缓慢,组织切片存活时间显著延长（P＜0.01）.结论 使用免疫抑制剂是预防同种异体牙移植免疫排斥反应的有效方案,可以使同种异体牙移植免疫排斥反应延迟,存活时间延长.     

Complement C4d deposition in transplanted kidneys: preliminary report on long-term graft survival

Abstract:  The effects of antibody-mediated rejection on long-term graft survival have not been fully investigated. The aim of this study is to clarify the influence on long-term survival of deposition of the complement split product C4d in allografts using polyclonal anti-C4d antibody. Inclusion criteria were recipients who underwent graft biopsy during acute deterioration of graft function within the first 2 yr after transplantation. Patients whose graft did not survive more than 1 yr and who received graft from an human leucocyte antigen (HLA)-identical sibling or an ABO-incompatible donor were excluded. Among the 92 recipients investigated, 22 (23.9%) had peritubular capillary C4d deposition, 15 (16.3%) had glomerular capillary C4d deposition and seven (7.6%) had both peritubular and glomerular capillary C4d deposition. Twenty of these 22 patients revealed acute cellular rejection, including borderline changes. There was no significant relationship between pathological severity of acute rejection and presence or absence of peritubular capillary C4d deposition. Graft survival was inferior in patients with peritubular capillary C4d deposition to that in patients without C4d deposition (p = 0.0419). Graft survival in patients with glomerular C4d deposition did not differ from that in patients without C4d deposition. In conclusion, C4d deposition in peritubular capillaries has a substantial impact on long-term graft survival.     

Renal allograft C4d deposition in Chinese: Hong Kong perspective

Background: Acute rejection constitutes a significant proportion of renal allograft loss. Peritubular capillary deposition of C4d has been recognized as the footprint of humoral alloimmunity and proven to be a sensitive and specific marker for humoral rejection in the appropriate clinical context. Its presence in indication biopsies is the most important independent risk factor for graft failure. Data are, however, scarce among Chinese subjects. Methods: We retrospectively reviewed all renal graft biopsies performed from 1 April 2002 to 31 March 2006 for unexplained acute renal dysfunction or delayed graft function. Renal outcomes were assessed at the time of renal biopsy and at 1 month, 3 months, 6 months and 1 year afterwards. Survival was assessed by Kaplan–Meier analysis. Multivariate analysis was used to determine if C4d positivity is an independent risk factor for poor renal outcome. Results: Fifty‐two biopsies were included, of which 16 were positive for peritubular capillary C4d. Peritubular capillary C4d was associated with lower glomerular filtration rate and higher serum creatinine at 6 and 12 months after renal biopsies. The C4d‐positive group fares worse in terms of death‐censored graft failure, doubling of serum creatinine and reaching 50% of glomerular filtration rate at the end of the study. Peritubular capillary C4d deposition was the only significant risk factor that predicts graft failure in multivariate analysis. Conclusion: Our findings confirmed the independent prognostic value of peritubular capillary C4d staining on renal allograft survival in Chinese.     

C4D deposition and positive posttransplant crossmatch are not necessarily markers of antibody-mediated rejection in renal allograft recipients

The aim of the study was to search for serologic, immunopathologic, and morphologic evidence of antibody-mediated rejection (AMR) among patients with acute renal allograft dysfunction. The study included 19 patients with episodes of acute rejection (ARE) within the first year after transplantation. All patients had negative crossmatch tests before transplantation. Patients underwent biopsy for histologic and C4d examinations. All patients were monitored for donor-specific HLA alloantibodies during the first posttransplant year. Complement-dependent cytotoxic crossmatches were performed with donor lymphocytes. In eight patients, the crossmatch test results changed to positive during ARE. In all biopsies except one with cortical infarction, we observed C4d staining (group 1). The biopsies of four patients showed histologic changes of AMR, and all of their grafts were lost. In one patient, cellular and vascular rejection (Banff II) were present; in two, Banff I; and in one, borderline lesions. These results were compared with 11 patients with ARE but negative posttransplant crossmatches and negative staining for C4d (group 2). The histologic findings in the biopsies of these patients were cellular interstitial and vascular rejection (Banff I and Banff II). With no features suggestive of AMR. During the first year after transplantation, the creatinine levels of group 1 patients, were significantly higher than group 2 patients. One-year graft survival was 50% in group 1 and 91% in group 2. CONCLUSIONS: C4d and a positive posttransplant crossmatch were not associated with histologic features of AMR in half of the ARE. Nevertheless, C4d deposition and positive posttransplant crossmatches correlated with allograft injury among renal transplant patients.     

Banff 07 Classification of Renal Allograft Pathology: Updates and Future Directions

The 9th Banff Conference on Allograft Pathology was held in La Coruna, Spain on June 23–29, 2007. A total of 235 pathologists, clinicians and scientists met to address unsolved issues in transplantation and adapt the Banff schema for renal allograft rejection in response to emerging data and technologies. The outcome of the consensus discussions on renal pathology is provided in this article. Major updates from the 2007 Banff Conference were: inclusion of peritubular capillaritis grading, C4d scoring, interpretation of C4d deposition without morphological evidence of active rejection, application of the Banff criteria to zero-time and protocol biopsies and introduction of a new scoring for total interstitial inflammation (ti-score). In addition, emerging research data led to the establishment of collaborative working groups addressing issues like isolated 'v' lesion and incorporation of omics-technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process.