移植肾活检：病理及组织学的早期诊断价值

背景：移植肾活检病理学组织学早期诊断意义重大,单中心回顾性研究临床诊断与治疗较少。 目的：通过对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断采取相应临床治疗方式,观察治疗效果,同时明确移植肾穿刺病理活检的安全性以及在临床诊治中的意义及其重要性。 方法：选取解放军第309医院器官移植中心202例肾移植患者为研究对象,其中80例为肾移植后移植肾功能延迟恢复,122例肌酐不明原因升高。在B超引导下应用活检穿刺针行移植肾穿刺活检,对活检组织标本予以相应染色和病理组织学观察,并进行相应的临床治疗。 结果与结论：穿刺组织中,除3例(1.5%)由于组织少难以诊断,其余病理诊断移植肾正常12例(5.9%),缺血再灌注损伤合并(或)急性肾小管坏死28例(13.9%),轻度钙调磷酸酶抑制剂类免疫抑制剂急性毒性损伤22例(10.9%),轻度钙调磷酸酶抑制剂类免疫抑制剂慢性毒性损伤12例(5.9%),超急性排斥反应1例(0.5%),疑为急性排斥反应29例(14.4%),急性T细胞性排斥反应34例(16.8%),急性抗体介导性排斥反应19例(9.4%),慢性T细胞介导排斥反应16例(7.9%),慢性T细胞介导排斥反应伴急性T细胞介导性排斥反应12例(5.9%),慢性抗体介导性排斥反应3例(1.5%),高血压因素4例(2.0%),间质纤维化和肾小管萎缩,未发现特定致病因素所致病变2例(1.0%),缺血性坏死2例(1.0%),移植后肾病复发３例(1.5%),C4d免疫组化染色阳性23例(11.4%),未发现患者及移植肾的不良反应。     

移植肾穿刺活组织检查：72例的病理及临床分析

背景：肾移植后慢性排斥反应及各种移植肾病变是移植肾失功能的常见原因,但对移植肾予以准确评估往往非常困难,活检仍是目前的主要手段。 目的：分析肾移植后出现合并症时移植肾穿刺活检的病理结果。 方法：对72例移植肾进行肾穿刺活组织检查,并进行病理诊断及分类,结合移植后情况进行分析。 结果与结论：72例中发生急性细胞介导性排斥反应35例,急性抗体介导性排斥反应12例,移植肾急性药物毒性损伤10例,慢性T细胞介导性排斥反应6例,慢性抗体介导性排斥反应2例,急性肾小管坏死4例,慢性移植肾肾病3例。移植肾组织活检的病理报告与穿刺前临床诊断的符合率在75%以上。移植肾穿刺活检未发生明显的不良反应。提示移植肾活检安全可靠,对肾移植后难以根据临床化验资料作出准确判断肾脏损害的并发症及治疗方案的选择有极为重要的指导意义。     

肾移植后移植肾功能的延迟恢复

背景：移植肾功能延迟恢复是肾移植常见的并发症,充分探究其发生的危险因素,及时预防与对应综合治疗是肾移植成功的关键。 目的：探讨肾移植后移植肾功能延迟恢复发生的病因及治疗方法。 方法：回顾性分析2000-12/2011-01在武警后勤学院肾移植中心明确诊断为肾移植后肾功能延迟恢复108例患者的临床资料,均为尸肾移植,给予相应治疗,观察临床疗效并综合分析出现肾功能延迟恢复的原因。 结果与结论：发生肾移植后移植肾功能延迟恢复的病因包括急性排斥反应52例(48.2%),急性肾小管坏死45例(41.5%);动脉吻合口狭窄5例(4.6%),输尿管梗阻3例(2.8%),环孢素A中毒肾病6例(5.6%)。89例患者经治疗后移植肾功能恢复正常,12例血肌酐稳定在200 μmol/L左右,2例因应用抗淋巴细胞球蛋白后并发肺部感染死亡,5例应用甲基强的松龙冲击治疗后移植肾功能未好转而恢复血液透析治疗。提示急性排斥反应及急性肾小管坏死是引起肾移植后肾功能延迟恢复的主要因素,应采取综合治疗措施积极纠正。     

肾移植术后超延迟肾功能恢复15例治疗体会

背景：肾脏移植患者急性排斥反应已不再成为术后的主要并发症,延迟肾功能恢复和慢性移植肾肾病仍然是移植患者术后需要面对的问题。 目的：总结分析15例术后发生超延迟肾功能恢复的肾移植患者资料,探讨临床经验及治疗对策。 方法：对肾移植后发生超延迟肾功能恢复患者15例进行回顾性分析。15例患者移植后均采用常规剂量的半量(环孢素A 3.0~4.0 mg/kg,他克莫司0.5~1 mg/kg),并定期监测血药浓度,随时调整免疫用药剂量,采用血液透析/连续性肾脏替代治疗。分析超延迟肾功能恢复诱因,患者观察患者肾功能恢复情况。 结果与结论：术中低血压、供肾热缺血时间过长、早期急性排斥反应、环孢素中毒、外科并发症、动脉粥样硬化致移植肾血液灌流不足可能为患者超延迟肾功能恢复的诱因。患者术后由少尿期开始进入多尿期时间最长者为108 d,平均32~108 d。肾功能正常8例(血清肌酐78~135 μmol/L),肾功能轻度异常5例(血清肌酐135~300 μmol/L),血清肌酐> 300 μmol/L者2例。随访时间最长1例11年,至今移植肾功能正常。结果提示,肾移植后尽早行移植肾穿刺活检及移植肾彩超,根据结果采取综合治疗并制订个体化治疗方案可以使大多数的患者移植肾功能恢复正常。     

尿单核细胞趋化蛋白1与肾移植后急性排斥反应:有相关性吗?

背景:目前移植肾急性排斥反应依然是导致慢性排斥反应和移植物功能损伤的危险因素,如何无创、快速、准确地进行诊断并及时治疗尤为重要。目的:通过检测尿液中单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)水平变化,并结合部分肾组织活检病例,探讨尿MCP-1在肾移植后急性排斥反应早期诊断及治疗后的表达。方法:选择2008-10/2009-02在郑州人民医院肾病移植科住院治疗的慢性肾衰竭患者62例,均接受同种异体肾移植,肾功能稳定组为肾移植后肾功能稳定的42例患者,急性排斥组为肾移植后发生急性排斥反应的20例患者,以同期在郑州人民医院体检中心检查肾功能正常且自愿留取尿样的10例健康人作为对照组。所用肾移植患者均给予常规免疫抑制方案,另外急性排斥组给予抗淋巴细胞免疫球蛋白或甲基强的松龙强化冲击治疗。应用双抗体夹心酶联免疫吸附试验检测尿MCP-1质量浓度变化。结果与结论:与对照组比较,肾功能稳定组尿MCP-1质量浓度无明显变化(P0.05),急性排斥组尿MCP-1质量浓度显著升高(P0.01)。与治疗前比较,急性排斥组20例患者经强化治疗后尿MCP-l质量浓度均显著降低(P0.01),其中17例临床症状缓解、辅助检查恢复正常,尿MCP-1质量浓度接近对照组,3例无效,尿MCP-1质量浓度高于对照组。肾穿刺活检8例,肾脏病理提示均为移植肾急性排斥反应,与急性排斥组治疗前尿MCP-1质量浓度基本相似(P0.05)。提示尿液中MCP-1水平可早期无创性诊断肾移植后急性排斥反应,可无创性监测治疗效果,其与肾移植后急性排斥反应时肾脏病理损伤可能存在相关性。     

移植肾穿刺病理组织中抗体介导的排斥反应

背景：体液性排斥以激素耐受和难治性为其显著的特点,常常发生在免疫高敏的受者身上。 目的：对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断观察抗体介导性排斥反应的治疗效果,分析移植肾穿刺病理活检的安全性。 方法：选取肾移植后有移植肾穿刺活检指征的患者84例,在B超引导下应用BARD(美国)活检穿刺针行移植肾穿刺活检,活检组织行常规苏木精-伊红染色,组织化学染色,同时常规行C4d免疫组织化学染色,依据Banff’05标准进行病理分型,根据病理状态明确诊断进行相应的临床治疗,观察治疗效果。 结果与结论：84例患者除1例由于组织少难以诊断,其余病理诊断移植肾超急性排斥反应1例,急性抗体介导性排斥反应5例,慢性抗体介导性排斥反应2例,C4d免疫组织化学染色阳性16例。经过治疗8例抗体介导性排斥反应患者中4例移植肾功能得以恢复,3例未恢复,1例移植肾失功,移植肾切除。患者无不良反应发生。结果表明移植肾穿刺病理活检对移植肾无不良影响。     

肾移植后急性体液性排斥反应的治疗

背景：肾移植后急性体液性排斥反应是一类人类白细胞抗原抗体介导的排斥反应,常导致移植物丧失功能。目前,强效免疫抑制剂和B淋巴细胞抑制剂的应用使急性体液性排斥反应的逆转率明显提高。 目的：探讨肾移植后急性体液性排斥反应的治疗方案。 方法：对20例发生急性体液性排斥反应的肾移植受者进行回顾性分析,患者给予抗胸腺球蛋白、蛋白A免疫吸附和大剂量丙种球蛋白联合治疗,所有患者均在蛋白A免疫吸附初次治疗前和末次治疗后留血标本测定群体反应性抗体和血清免疫球蛋白IgG,IgA,IgM。 结果与结论：20例患者急性体液性排斥反应均有效逆转。随访48个月,1例患者在移植后5个月时因合并严重的肺部感染而停用免疫抑制剂,继而发生剧烈的急性排斥反应而行移植肾切除,恢复血液透析,其余患者移植肾功能良好,至随访终点时平均血肌酐浓度为(132.6±44.2)µmol/L。提示,抗胸细胞球蛋白联合蛋白A免疫吸附和大剂量丙种球蛋白能够有效逆转肾移植后急性体液性排斥反应,成功率高,并发症少,且完全逆转的急性体液性排斥反应并不影响移植肾的预后。     

尿趋化因子IP-10和Fractalkine在移植肾急性排斥反应早期诊断中的应用

背景：相关研究已证实,趋化因子IP-10、Fractalkine在器官移植后急性排斥反应过程中发挥着重要的作用。 目的：检测尿液中IP-10和Fractalkine水平变化,并结合肾组织活检病理,探讨尿液中IP-10 和Fractalkine在移植肾急性排斥反应早期诊断中的意义。 方法：106例同种异体肾移植患者,根据移植后临床表现、实验室检查及肾穿刺组织病理学检查结果,分为急性排斥反应组(n=16)和非急性排斥反应组(n=90);另选择健康志愿者作为正常对照组。用双抗体夹心酶联免疫吸附试验检测尿IP-10和Fractalkine浓度变化。 结果与结论：急性和非急性排斥反应组患者在移植后的尿IP-10及Fractalkine的表达水平均较移植前明显升高,但非急性排斥反应组在移植后7 d呈下降趋势,至第11天降至移植前水平,而急性排斥反应组则持续高表达,IP-10在移植后第1天和Fractalkine在移植后第3天即与急性排斥反应组比较,差异有显著性意义(P < 0.05)。提示,肾移植后尿液中IP-10和Fractalkine水平的检测对于急性排斥反应发生的早期诊断和早期治疗具有重要意义。     

大鼠肾移植急性排斥反应过程中 IL-17 表达及其意义

目的:探讨IL-17在大鼠肾移植急性排斥反应过程中的表达特点及其意义。方法:将大鼠随机分为正常对照组、同系基因对照组、同种异体移植组、免疫抑制剂干预组,并建立肾移植急性排斥反应模型,用RT-PCR及免疫组织化学方法检测急性排斥时IL-17在肾组织中的表达。结果:同种异体移植组在移植后第3天、5天和7天,移植肾IL-17均明显升高,与其他组相比,均有统计学意义(P0. 05),其中以第5天为最高,差异具有统计学有意义(P0. 05)。结论:IL-17参与了大鼠肾移植急性排斥反应的发生,并为早期事件,IL-17检测可能为人类肾移植早期急性排斥反应的诊断和治疗提供理论依据。     

丹参注射液在肾移植后急慢性排斥反应中的作用

背景：临床观察,肾移植后发生急、慢性排斥反应时单用甲基强的松龙针冲击,尿蛋白、血肌酐值改善不明显,若加用丹参注射液静脉滴注,可使移植肾功能恢复更迅速。 目的：观察丹参注射液对肾移植后急慢性排斥反应肾功能恢复的影响。 方法：肾移植后发生急性排斥反应患者180例,慢性排斥反应患者140例,分别随机分成两组,对照组单纯应用常规甲基强的松龙冲击治疗3 d,治疗组在此基础上加用丹参注射液静脉滴注15 d。 结果与结论：与治疗前相比,急慢性排斥反应两组肾功能恢复指标均有明显改善,差异有显著性意义(P < 0.05);治疗组比对照组肾功能指标改善更明显(P < 0.05)。且治疗组延长了凝血酶原时间和活化部分凝血活酶时间(P < 0.05)。结果证实了肾移植患者发生急慢性排斥反应后在常规处理基础上加用丹参注射液能明显改善移植肾功能。     

Arteriolitis in renal transplant biopsies is associated with poor graft outcome

AIMS: The Banff 1997 classification of renal allograft pathology identifies arteriolitis as a finding of uncertain significance. We sought to improve our understanding of arteriolitis by correlating its occurrence with histopathological and clinical parameters. METHODS AND RESULTS: Twenty allograft kidney biopsies from 19 patients, showing arteriolitis, were identified. Arterioles were defined as small vessels with: (1) wall thickness of 1-3 myocytes; (2) diameter less than one-third of an adjacent glomerulus; and (3) discontinuous or absent elastica. Arteriolitis was defined as mural infiltration by lymphocytes. Other histological findings were categorized according to the Banff 1997 working formulation. Ten biopsies (50%) showed type IIA rejection, seven (35%) showed type I rejection, and three (15%) showed borderline change. Two patients with borderline change had acute rejection in the next biopsy. None of the seven patients with type I rejection had previous or subsequent type II rejection on biopsy. A total 11/20 biopsies (10/19 patients) showing arteriolitis had type IIA rejection in the index or next biopsy. On follow-up, graft loss due to rejection occurred in 5/19 (26%) patients (median 126 days); all had shown type IIA rejection on a previous biopsy. Chronic allograft nephropathy developed in a further 4/19 (21%) patients (median 157 days), of whom three had shown only type I rejection on biopsy. CONCLUSION: Arteriolitis is associated with acute rejection, often type II rejection, and is associated with poor graft outcome. Other causes of arteriolitis were not encountered in this series.     

Frozen-section analysis of allograft renal biopsy specimens. Reliable histopathologic data for rapid decision making

Rapid tissue diagnosis during acute events associated with renal transplantation is often necessary to permit immediate decisions regarding initiation or modification of therapy. To achieve this, we performed frozen section analyses with cryoprotected alcoholic Bouin's-fixed tissue, which permits evaluation within 2.5 hours. During a 30-month period, 200 allograft biopsies were performed; 68 frozen sections were obtained when deemed necessary by the clinical team. We compared frozen-section diagnoses with those following regular evaluation of the biopsy specimen. Agreement in diagnoses occurred in 61 (88.4%) of 69 specimens. Acute rejection was the dominant diagnosis (n = 39); others were acute tubular necrosis, cyclosporine toxicity, chronic rejection, and infection. Major misdiagnoses included acute vascular processes (three capillary and/or venous thromboses and one vascular inflammation); acute cellular rejection was missed in two cases, reflecting a sampling error. Secondary diagnoses not of immediate therapeutic importance were detected in seven frozen sections and missed in nine. These included chronic glomerulopathies, nephrosclerosis, and mild chronic rejection. Although acute vascular phenomena may be difficult to recognize in frozen sections, we conclude that allograft biopsy frozen-section analysis is a valuable part of the care of transplant recipients.     

肾移植后急性体液排斥反应：5年同一机构296例随访*

背景：肾移植后急性体液排斥反应虽然发生率不高,但对移植物功能恢复可造成严重影响,是移植物早期丢失的主要原因。 目的：分析肾移植后急性体液排斥反应早期诊断和防治的意义。 方法：选择接受肾移植后规律随访的受者296例,其中移植前群体反应性抗体阳性受者26例,阴性受者270例。酶联免疫吸附试验动态监测肾移植受后外周血中的群体反应性抗体和供者特异性抗体,免疫组织化学染色观察穿刺活检组织中C4d的沉积及浸润淋巴细胞表面分子标记,按Banff 2005标准结合临床相关指标诊断急性体液排斥反应。 结果与结论：26例移植前群体反应性抗体阳性受者中6例(23%)移植后发生了急性体液排斥反应,270例阴性受者中19例(7%)发生了急性体液排斥反应,差异有显著性意义(P < 0.01)。发生急性体液排斥反应的患者中22例(88%)外周血清中检测到供者特异性抗体,271例无急性体液排斥反应的患者中仅1例检出供者特异性抗体,差异具有显著性意义(P < 0.01)。急性体液排斥反应受者中C4d阳性率为80%,未发生急性体液排斥反应的患者C4d阳性率仅为6.7%,差异具有显著性意义(P < 0.001)。肾移植后早期监测群体反应性抗体和供者特异性抗体水平,通过穿刺活检观察移植肾组织中的C4d沉积情况,可及时诊断急性体液排斥反应,有效改善移植物功能并提高移植物存活率。关键词：肾移植;供者特异性抗体;急性体液排斥反应;C4d;利妥昔单抗  doi:10.3969/j.issn.1673-8225.2012.18.005 中图分类号: R617  文献标识码: A   文章编号: 1673-8225(2012)18-03249-06     

The clinical and pathologic implications of plasmacytic infiltrates in percutaneous renal allograft biopsies

Plasmacytic infiltrates in renal allograft biopsies are uncommon and morphologically distinctive lesions that may represent variants of acute rejection. This study sought significant clinical and pathologic determinants that might have influenced development of these lesions and assessed their prognostic significance. Renal allograft biopsies (n = 19), from 19 patients, with tubulointerstitial inflammatory infiltrates containing abundant plasma cells, composing 32 +/- 8% of the infiltrating mononuclear cells, were classified using Banff '97 criteria. Clonality of the infiltrates was determined by immunoperoxidase staining for kappa and lambda light chains and polymerase chain reaction for immunoglobulin heavy-chain gene rearrangements, using V(H) gene framework 3 and JH consensus primers. In situ hybridization for Epstein-Barr virus encoded RNA (EBER) was performed in 17 cases. The clinical features, histology, and outcome of these cases were compared with kidney allograft biopsies (n = 17) matched for time posttransplantation and type of rejection by Banff '97 criteria, with few plasma cells (7 +/- 5%). Sixteen of 19 biopsies (84%) with plasmacytic infiltrates had EBER-negative (in 14 cases tested) polyclonal plasma cell infiltrates that were classifiable as acute rejection (types 1A [4], 1B [10], and 2A [2]). These biopsies were obtained between 10 and 112 months posttransplantation. Graft loss from acute and/or chronic rejection was 50% at 1 year and 63% at 3 years, and the median time to graft failure was 4.5 months after biopsy. There was no significant difference in overall survival or time to graft failure compared with the controls. Three of 19 biopsies (16%) had EBER-negative polyclonal plasmacytic hyperplasia, mixed monoclonal and polyclonal polymorphous B cell hyperplasia, and monoclonal plasmacytoma-like posttransplantation lymphoproliferative disease (PTLD) and were obtained at 17 months, 12 weeks, and 7 years after transplantation, respectively. Graft nephrectomies were performed at 1, 19, and 5 months after biopsy, respectively. Plasmacytic infiltrates in renal allografts comprise a spectrum of lesions from acute rejection to PTLD, with a generally poor prognosis for long-term graft survival.     

Peritubular capillary C4d deposition in chronic allograft dysfunction

Peritubular capillary (PTC) C4d staining represents a marker for acute humoral rejection, however, the impact of positive staining on chronic allograft dysfunction has received little attention. Ninety-three renal allograft biopsies from 93 patients were selected from a total of 174 renal allograft biopsies, which were obtained 6 months or more after transplantation (median: 89 months). Fresh frozen renal tissue was stained with monoclonal antibody against C4d. Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in 40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24). When the samples were divided according to C4d positivity, the C4d (+) group had a higher proportion of acute rejection than the C4d (-) group. However, no significant difference was observed between the two groups in terms of the prevalence of chronic rejection. Degrees of histological injury including tubulitis, interstitial inflammation and interstitial fibrosis were not significantly different between C4d (+) and C4d (-) groups. However, the 2-year graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (-) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with late acute rejection, but not with chronic rejection based on conventional morphologic criteria in patients with chronic allograft dysfunction.     

Arcuate and interlobular phlebitis in renal allografts

Intimal arteritis in the renal allograft has a well-documented adverse effect on graft outcome. In contrast, venulitis is currently considered an innocuous finding, based largely on observations of thin-walled intermediary venules. Arcuate and interlobular veins have not been studied specifically. These veins have well-developed muscular walls, and inflammation at this level (phlebitis) could significantly alter renal hemodynamics. We studied the clinicopathologic correlates of arcuate and interlobular phlebitis in 31 renal allograft biopsy specimens. Phlebitis was seen in conjunction with borderline changes suggestive of acute cellular rejection (13 cases), or acute rejection Banff grade 1A (7 cases), Banff grade 1B (6 cases), Banff grade 2A (4 cases), and Banff grade 2B (1 case). Clinical follow-up (average 323 +/- 460 days) showed no adverse effects of phlebitis as judged by temporal changes in serum creatinine and the grade of chronic allograft nephropathy in follow-up biopsies. Thus it appears that arcuate and interlobular phlebitis in allograft biopsy specimens does not add prognostic information beyond that provided by conventional Banff criteria. However, this lesion frequently coexists with changes suggestive or diagnostic of acute cellular rejection, and intimal arteritis may be seen concurrently in up to 16% of cases.     

肾移植受者血清sFas和sFasL变化及在早期急性排异反应预测中的应用

背景：细胞凋亡在移植免疫和移植物功能丧失发生过程中起十分重要的作用,其中Fas/FasL系统被认为是细胞凋亡参与肾移植的急性排异反应过程的主要途径之一。 目的：分析肾移植受者术后血清sFas和sFasL水平变化及其在预测早期急性排异反应中的应用价值。 方法：肾移植受者80例分为肾功能稳定组(49例)、急性排斥反应组(23例)和环孢素A中毒组(8例)。另选择性别、年龄与肾移植受者相匹配的健康体检者50例为对照组。肾移植受者术后均常规使用环孢素A+硫唑嘌呤+泼尼松三联免疫抑制治疗。发生急性排斥反应时给予每日甲基强的松龙6~8 mg/kg冲击治疗,3 d为1个疗程。采用ELISA法检测患者手术前后的血清sFas和sFasL水平。 结果与结论：肾移植组患者手术前的血清sFas和sFasL水平均明显高于对照组(P  < 0.05)。急性排斥反应组血清sFas、sFasL水平高于相同时间段肾功能稳定组(P < 0.05)。环孢素A中毒的肾移植患者术后各时间点血清sFas、sFasL水平变化与肾功能稳定组基本相同,差异无显著性意义。提示动态监测血清sFas、sFasL水平可能对早期诊断及鉴别诊断肾移植急性排斥反应具有重要参考价值。     

肾移植术后血清sICAM-1和sVCAM-1的动态监测及临床意义

目的：探讨肾移植术后监测血清可溶性细胞问粘附分子-1(sICAM-1)和可溶性血管细胞粘附分子-1(sVCAM-1)的临床意义。方法：采用ELISA法，动态监测86例肾移植患者手术前后血清sICAM-l和sVCAM-1的变化。结果：移植术前sICAM-1、sVCAM-l与对照组无显著性差别，术后均明显升高，于第3天时达到高峰，l周至2周后降至术前水平。发生急性排斥反应前l-3天血清sICAM-1、sVCAM-1即开始升高，抗排斥治疗有效后逐渐下降。并发感染时sICAM-1、sVCAM-l显著升高，CsA中毒时无明显变化。结论：动态监测血清sICAM-1、sVCAM-l可做为早期辅助诊断急性排斥反应的免疫学指标，有助于急性排斥反应与CsA肾中毒的鉴别。