肾组织活检在移植肾功能损害的诊断与鉴别诊断中的价值

目的 探讨移植肾组织活检在移植肾功能损害的诊断与鉴别诊断中的价值。方法 对158例移植肾组织活检资料进行回顾分析。结果 158例中以急性排斥反应多见,共55例（34．8％）,移植肾改变35例（22．2％）,临界改变32例（20．2％）,慢性排斥反应13例（8．3％）,系膜增生性病变13例（8．3％）,急性肾小管坏死6例（3．8％）,新月体性肾炎、溶血性尿毒综合征和毛细血管内增生性肾炎各1例（0．6％）;血中环孢素A的浓度与急性排斥反应的发生率无明确正相关关系;临床诊断与肾组织活检结果尚存在一些差异。结论 肾组织活检对明确诊断及提高临床诊断的正确率及选择治疗方案有重要价值。     

肾移植2508例次临床总结

目的总结肾移植的临床经验,探讨影响移植术后人／肾存活的因素,提高长期存活率。方法回顾性总结1979年1月～2008年6月2508例次肾脏移植资料,分析患者术前状况、组织配型、群体反应性抗体（PRA）、供肾的切取、灌注、热冷缺血时间、植肾技术、术后并发症的发生、不同免疫抑制剂方案、再次移植等因素对移植效果及人／肾存活率的影响。结果①移植效果：总体人／肾存活率81．4％／76．3％;近10年来,1、5、10年人／肾存活率（%）分别为：96．5／93．2、88．6／81．6和74．7／71．3;186例活体亲属供者随访均健康存活,受者1年人／肾健康存活率98．5％／95．5％;②排斥反应：超级排斥反应发生率0．7％,急性排斥反应（AR）发生率13．7％,近十年来急性排斥反应（AR）发生率7．4％;③术后并发症：发生各种感染787例,急性肾小管坏死（ATN）275例,药物毒副作用590例,肾动脉及肾破裂19例;晚期输尿管梗阻39例,恶性肿瘤28例;④死亡原因：前三位的分别是感染占47．3％,心脑血管并发症占34．8％,肝功能衰竭占10．9％。结论充分的术前准备、良好的HLA配型、加强PRA检测是提高存活率的基础;高质量的供肾和娴熟的移植技术是肾移植成功的重要保证;科学、合理、个体化的应用免疫抑制剂是移植后治疗的重点,环孢素A（CsA）或他克莫司（FK506）、霉酚酸酯（MMF）、泼尼松（Pred）三联是目前首选的免疫抑制治疗方案。加强感染的早期监测、预防性治疗是术后早期治疗的另一关键．加强患者的随访,提高患者的依从性,对指导肾移植受者长期存活具有重要价值。     

肾移植受者蛋白尿病因分析及临床处理

目的探讨肾移植受者蛋白尿的病因和临床对策。方法对广州医学院第二附属医院2006年7月至2010年8月随访中出现蛋白尿的103例肾移植受者进行移植肾穿刺活组织检查（简称活检）,根据病理学诊断进行相应的临床治疗。结果 103例移植肾活检中急性排斥反应32例,慢性排斥反应25例,肾小球肾炎30例（其中IgA肾病12例）,肾小管-间质损伤7例,其他9例（包括肾小球轻微病变6例,糖尿病肾损害3例）。经过分类治疗后70.9%（73/103）受者蛋白尿逆转,肾功能维持稳定。结论排斥反应和原有肾疾病复发是导致肾移植受者蛋白尿的主要原因,移植肾活检是早期明确蛋白尿病因的有效手段,根据病理学诊断结果进行分类治疗可取得良好临床效果。     

血小板/内皮细胞粘附分子在急性排斥反应时表达的研究

应用免疫级化SP法和计算机图像分析系统观察分析18例急性排斥反应时移植肾活检标本中血小板／内皮细胞粘附分子（PECAM－1，CD31）的表达。结果显示急性排斥反应时肾小球毛细血管内皮细胞中PECAM－1阳性反应强度较正常明显减低或由阳性转为阴性，而在肾小管上皮中表达增强；PECAM－1与HLA－DR抗原在肾小球和肾小管中的表达呈平行关系。提示细胞粘附分子PECAM－1对移植肾急性排斥反应有一定诊断意义。     

急性排斥反应时移植肾组织中程序性死亡配体-1及其受体的表达

目的探讨急性排斥反应时移植肾组织中程序性死亡配体-1(PD-L1)及程序性死亡-1(PD-1)的表达及其与肾小管间质病理损害程度的关系。方法当肾移植患者发生急性排斥反应并经病理检查确认时,采取移植肾组织,以免疫组化和原位杂交染色法,观察肾组织中PD-L1和PD-1的表达,分析PD-L1阳性强度与肾小管-间质PD-1阳性细胞数、肾小管间质病理损害程度的关系。以正常肾组织为对照。结果急性排斥反应时,移植肾组织中的PD-L1及PD-1的表达较正常组织增多、增强(P<0.01);肾小管PD-L1阳性强度与肾间质PD-1阳性细胞数呈正相关,与肾小管间质病理损害程度呈负相关。结论急性排斥反应时,PD-L1及PD-1的表达增强,它们可能在肾小管间质病理损害中起重要作用。     

肾移植术后移植肾功能延迟恢复的处理(附14例报告)

目的探讨肾移植术后移植肾功能延迟恢复（DGF）的原因及处理措施。方法通过对发生DGF的14例患者临床表现、血肌酐、环孢素A（CsA）血浓度、彩色多普勒超声、移植肾细针穿刺吸抽细胞学检查（FNAB）等分析，诊断移植肾静脉栓塞1例，CsA中毒性肾损害2例，急性肾小管坏死（ATN）6例，急性排斥反应（AR）5例。分别予血液透析、手术探查、调整免疫抑制剂种类或剂量等处理。结果1例移植肾静脉栓塞患者行移植肾切除术；13例患者9—27d尿量增多，术后1个月复查肾功能良好。结论DGF原因包括技术性并发症、CsA中毒性肾损害、ATN、排斥反应等，应结合临床表现及辅助检查，早期诊断，及早采取血液透析、手术探查、调整免疫抑制剂种类或剂量等措施，可取得良好效果。     

移植肾功能延迟恢复的临床诊治体会

目的．探讨肾移植术后移植肾功能延迟恢复（DGF）的病因及治疗方法。方法分析本组发生的43例肾移植术后DGF患者的临床资料，主要原因：急性排斥（AR）17例（39．5％），急性肾小管坏死（ATN）16例（37．2％），输尿管梗阻4例（9．3％），免疫抑制剂肾毒性4例（9．3％），动脉吻合口狭窄2例（4．6％）。经血液透析治疗16例，ATG／ALG或OKT3治疗12例，外科手术6例。结果36例肾移植术后8—113d（平均23．8d）肾功能恢复正常，2例肌酐在176—300μmol／L之间，4例恢复血透，1例死于肺部感染。结论AR和ATN是引起肾移植术后DGF的主要因素，术前严格配型、合理筛选受者及保证供肾质量等是成功的关键。     

亲属活体肾移植的临床分析和移植肾组织病理分析

目的 总结亲属活体肾移植后移植肾组织活检资料，并结合临床进行回顾性分析。方法亲属活体肾移植55例，其中有血缘的亲属供肾移植53例，夫妻间供肾移植2例。供、受者间HLA配型，1条单倍型相同者45例，2条单倍型相同者6例，5个抗原错配者3例，完全错配者1例。除1例采用腹腔镜取肾外，其余均采取开放手术取肾。供肾热缺血时间1～8min，冷缺血时间1～2h。术后应用环孢素A（或他克莫司）、硫唑嘌呤（或霉酚酸酯）及泼尼松预防排斥反应。结果 55例中，有10例接受16次移植肾活检，结果 4例次为急性排斥反应（Banff分级均为Ⅰ级），3例次经甲泼尼龙冲击治疗逆转，1例合并慢性移植肾肾病，治疗无效，恢复透析；3例次为移植肾退行性病变（其中2例合并急性环孢素A肾毒性损伤），2例减少环孢素A用量，并加用西罗莫司，效果良好，1例将环孢素A转换为西罗莫司，效果不佳，恢复透析；4例次为急性肾小管坏死，采用他克莫司和霉酚酸酯联合用药，并辅以透析治疗，肾功能恢复正常。结论 虽然亲属活体肾移植术后急性排斥反应和移植肾功能恢复延迟的发生率低，但仍应重视术后移植肾组织活检，将被动活检转为主动的计划性活检，以提高亚临床排斥反应的检出率。     

移植肾活组织检查在急性排斥反应预后判断上的价值

报告我院经肾活组织检查 (肾活检 )病理学诊断急性排斥反应 3 2例 ,并将急性排斥反应近期转归与肾活检病理学改变参数作相关性回顾分析 ,探讨肾活检在移植肾急性排斥反应预后判断上的价值。一、临床资料1988～ 1999年我院共行尸体肾移植术 4 0 0余例 ,经肾活检诊断急性排斥反应3 2例 ,其中男性 2 8例 ,女性 4例。年龄( 3 7± 7)岁。肾移植术后给予泼尼松、硫唑嘌呤和环孢素Ａ三联免疫抑制剂治疗 ,少数早期病例仅以前二者联合抗排斥。确诊急性排斥反应者给予甲泼尼龙0 .5～ 1.0 ｇ/ｄ静脉滴注 ,连续冲击 3ｄ ,酌情给 1～ 3个疗程 ,合用透析疗…     

1200次移植肾穿刺的并发症及临床意义分析

目的　分析移植肾穿刺术的临床意义及并发症 ,以促进移植肾活检术在肾移植患者中的广泛应用。方法　 1 994年 1月至 2 0 0 1年 1月行肾移植术的 590例患者 ,术后常规行移植肾活检术 ,肾功能短期内急剧恶化者急诊行肾穿刺活检术。采用斜角进针负压吸引法 ,对其并发症及肾活检组织病理学改变进行了分析。结果　 590例患者共行 1 2 0 0次肾穿刺术 ,穿刺成功率为 99.8% ,组织质量较好的占 81 .3 % ,光镜标本平均每份包含肾小球 (1 9.0± 9.0 )个。肾穿刺后肉眼血尿的发生率为1 .6 % ,肾周血肿的发生率为 0 .3 % ,经对症处理后缓解。出现出血并发症的患者肾组织病理学检查均有异常改变 ,包括急性肾小管坏死 (ATN) ,急性排斥反应 ,慢性排斥反应等。病情稳定患者的血清肌酐水平在肾活检后无明显的变化 .肾功能正常患者的肾活检组织病理检查发现异常的有 2 7.8% ,其中临界改变占 1 1 .9% ,动脉内膜炎占 4 .0 % ,急性排斥占 1 .4 % ,此外尚有少量的慢性排斥及间质非特异性细胞浸润。肾功能异常的患者中有 34 .9%肾组织病理表现为正常移植肾改变 ,30 .2 %的患者诊断为急性排斥 ,1 7.4 %患者诊断为临界改变 ,动脉内膜炎及ATN各占有 0 .3 %。结论　斜角进针负压吸引肾活检术在肾脏移植患者中应用成功率高 ,且较为安     

The contribution of adhesion molecule expression in donor kidney biopsies to early allograft dysfunction.

BACKGROUND: Renal allograft rejection is associated with the expression of adhesion molecules on vascular endothelial and tubular epithelial cells. METHODS: To assess whether the number of cell adhesion molecules expressed in donor kidneys can predict early rejection or delayed graft function, kidney biopsies from 20 living and 53 cadaveric kidney donors were obtained before engraftment into the recipients and the expression of the cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were determined by immunohistochemistry. RESULTS: All biopsies from living donors showed significantly lower expression of ICAM-1 and VCAM-1 compared to biopsies from cadaveric donors. There was no difference in the expression of adhesion molecules on tubular cells between transplants with primary function compared to allografts with early rejection in living donated kidneys (ICAM-1: 2+/-8 vs. 3+/-8%; VCAM-1: 9+/-7 vs. 1+/-1%), as well as in cadaveric kidneys (ICAM-1: 38+/-29 vs. 39+/-38%; VCAM-1: 55+/-27 vs. 48+/-29%). The expression of ICAM-1 molecules on tubular cells was determined to be a predictor for the occurrence of delayed graft function in cadaveric kidneys (ICAM-1: 65+/-24* vs. 38+/-29% delayed graft versus primary graft function). No delayed graft function occurred in recipients of living donated kidneys. CONCLUSIONS: These data suggest that adhesion molecule expression in donor biopsies is not a predictor for early allograft rejection, but can be used as a marker for the development of postischemic acute renal allograft failure.     

MIC expression in renal and pancreatic allografts

BACKGROUND: MHC class I chain-related antigen A (MICA) and MHC class I chain-related antigen B (MICB) are HLA class I related products of polymorphic MHC genes. Constitutive expression in normal tissue is limited to gut epithelium but can be induced in other epithelial cells by stress. Specific antibodies against MICA have been reported in the serum of patients who had rejected kidney allografts, suggesting a potential role for these molecules in transplant immunopathology. However, expression of MICA and MICB in transplanted organs has not been demonstrated. In this study, we report the expression of MICA and MICB in renal and pancreatic allograft biopsies, which were obtained due to clinical signs of rejection. METHODS: A monoclonal antibody directed against MICA and MICB was used to perform indirect immunohistochemistry on formalin fixed, paraffin embedded needle biopsies of kidney and pancreas allografts. The results of staining were then compared to the standard light microscopic evaluation of the biopsies for rejection. RESULTS: A total of 53 individual renal transplant biopsies and 19 pancreas transplant biopsies were assayed for expression of MIC. Histologically, renal biopsies were diagnosed as no rejection, acute tubular necrosis (ATN), acute rejection (AR), chronic rejection (CR), and acute and chronic rejection (ACR). No staining was observed in 7 of 10 kidneys showing no rejection. All 11 of the kidney biopsies with AR were positive, as were the 11 ATN cases, 9 of the 11 kidney biopsies with CR, and 7 of the 10 with ACR. The acini of normal, nontransplanted, pancreas, control specimen were consistently negative; however, islets were positive in all specimens. The acini and islets of five histologically normal pancreas biopsies were positive, as were the four biopsies with AR, seven biopsies with CR, and two with ACR. CONCLUSIONS: MICA and MICB are expressed in epithelial cells in allografted kidney and pancreas that show histologic evidence of rejection and/or cellular injury. In addition to previous findings of alloantibodies against MICA, expression of these gene products may play a role in allograft rejection.     

Natural history, risk factors, and impact of subclinical rejection in kidney transplantation

BACKGROUND: Subclinical rejection (SCR) is defined as histologically proven acute rejection in the absence of immediate functional deterioration. METHODS: We evaluated the impact of SCR in 961 prospective protocol kidney biopsies from diabetic recipients of a kidney-pancreas transplant (n=119) and one kidney transplant alone taken regularly up to 10 years after transplantation. RESULTS: SCR was present in 60.8%, 45.7%, 25.8%, and 17.7% of biopsies at 1, 3, 12, and greater than 12 months after transplantation. Banff scores for acute interstitial inflammation and tubulitis declined exponentially with time. SCR was predicted by prior acute cellular rejection and type of immunosuppressive therapy (P<0.05-0.001). Tacrolimus reduced interstitial infiltration (P<0.001), whereas mycophenolate reduced tubulitis (P<0.05), and the combination effectively eliminated SCR (P<0.001). Persistent SCR of less than 2 years duration on sequential biopsies occurred in 29.2% of patients and was associated with prior acute interstitial rejection (P<0.001) and requirement for antilymphocyte therapy (P<0.05). It resolved by 0.49 +/- 0.33 years and resulted in higher grades of chronic allograft nephropathy (CAN, P<0.05). True chronic rejection, defined as persistent SCR of 2 years or more duration and implying continuous immunologic activation was found in only 5.8% of patients. The presence of SCR increased chronic interstitial fibrosis, tubular atrophy, and CAN scores on subsequent biopsies (P<0.05-0.001). SCR preceded and was correlated with CAN (P<0.001) on sequential analysis. CONCLUSIONS: Histologic evidence of acute rejection in the absence of clinical suspicion resulted in significant tubulointerstitial damage to transplanted kidneys and contributed to CAN.     

Risk factors for chronic allograft nephropathy after renal transplantation: a protocol biopsy study

BACKGROUND: Chronic allograft nephropathy (CAN) leads to chronic allograft dysfunction and loss. Regular renal transplant biopsies may be useful to find risk factors for CAN. METHODS: We carried out 688 protocol biopsies in 258 patients at 6, 12, and 26 weeks after renal transplantation. Patients with signs of CAN in the biopsy 3 (N= 70, CAN group), and those without (N= 120, non-CAN group), were compared. RESULTS: Chronic tubulointerstitial changes increased from biopsy 1 to 3 (5% vs. 37%, P < 0.0001). Fifty-six of 190 patients had acute rejection within 6 months (30%), 33 of which were found in protocol biopsies (17%). On univariate analysis, the CAN group had CAN more often at biopsy 2 than the non-CAN group (23% vs. 4%, P < 0.0001), had a lower calculated creatinine clearance at biopsy 1 and 2 (49.4 +/- 25.8 vs. 57 +/- 20.2 mL/min, P= 0.01; 47.3 +/- 21.2 vs. 57.9 +/- 19.5 mL/min, P= 0.001, respectively), had a living donor less often than a brain dead donor (7% vs. 18%, P= 0.045), had a longer cold ischemia time (17.4 +/- 7 vs. 14.9 +/- 8.1 hours, P= 0.04), and had arterionephrosclerosis more often (24% vs. 12%, P= 0.02). On multivariate analysis, the differences in CAN at biopsy 2 (P= 0.001) and lower GFR at biopsy 2 (P= 0.002) were confirmed; in addition, nephrocalcinosis (P= 0.006) and acute rejection (P= 0.046) were found to occur more often. CONCLUSION: Chronic tubulointerstitial changes develop early after renal transplantation and are associated with reduced kidney function. Risk factors for CAN are arterionephrosclerosis (donor-related), nephrocalcinosis (related to preexisting hyperparathyroidism), a long cold-ischemia time (ischemia-perfusion-related), and acute rejection. Renal functional decline precedes morphologic changes of CAN, expressed as tubular atrophy and interstitial fibrosis.     

TGF-beta1 expression in renal allograft rejection and cyclosporine A toxicity

BACKGROUND: To assess short- and long-term influence of the TGF-beta1 on renal allografts. METHODS: Expression of TGF-beta1 and TNF-alpha, and the proportion of macrophages and eosinophils in interstitium were evaluated in 64 cases including five cases with nonrejected kidneys (NRK), 18 cases with acute rejection (AR), 26 cases with chronic allograft nephropathy (CAN), and 15 cases with acute cyclosporine A (CsA) toxicity. Follow-up biopsies of all cases with AR and CsA toxicity were evaluated for development of interstitial fibrosis (IF) and graft atherosclerosis (GAS). Additionally, influence of tubular-TGF-beta1 expression on graft function during 6 months after the diagnostic biopsy was evaluated. RESULTS: A significant differences was seen between rejected kidneys and acute CsA toxicity in regards of tubular TGF-beta1 expression that patients with CsA toxicity exhibited significantly higher grade of tubular TGF-beta1 expression than patients with AR (P<0.05) and CAN (P<0.05). A significant difference was found between the grades of tubular TGF-beta1 expression in regards to graft function of cases with AR and CsA toxicity (P<0.05). Higher grade tubular TGF-beta1 expression showed better graft function during 6 months. Besides the degree of renal TGF-beta1 expression was positively correlated with development of diffuse IF and GAS (P<0.05) that the risk of the IF and GAS was higher in cases with grade 2 renal TGF-beta1 expression. CONCLUSIONS: Despite the short-term posttransplantation tubule-repairing effects of TGF-beta1, the overall effects of TGF-beta1 in the kidney seem to be negative that increased expression of TGF-beta1 promotes IF and vasculopathy associated with CAN.     

The role of C4d immunostaining in the evaluation of the causes of renal allograft dysfunction.

BACKGROUND: Renal biopsy is the gold standard for diagnosis of acute rejection in renal transplant recipients. The Banff (1997) classification was revised in 2003 incorporating morphological criteria and C4d immunostaining for the diagnosis of acute antibody-mediated rejection. AIMS: The aim of this study was to evaluate the role of histomorphology and C4d immunostaining in indicated renal allograft biopsies with a clinical follow-up for a minimum duration of 1 year. MATERIAL AND METHODS: Histological analysis and C4d immunostaining were performed on 132 needle core biopsies and 2 nephrectomy specimens from 107 patients from July 2004 to June 2005. RESULTS: Histological analysis revealed 59 cases of acute rejection, 10 biopsies of acute tubular necrosis, 41 cases of chronic allograft nephropathy (CAN), either alone or in combination with other diseases, and 18 biopsies of normal morphology. There were four cases of BK nephropathy (BK N) and eight cases had miscellaneous diagnoses. C4d immunostaining was performed on 126 biopsies. Overall, the prevalence of C4d positivity was 45% (57 of 126). Fifty-five percent (28 of 51) of the cases of acute rejection showed C4d positivity including 81% of presumptive antibody-mediated rejection (P-AbAR), 20% acute cellular rejection and 58% acute cellular rejection + P-AbAR. Overall C4d positivity was 37% in chronic allograft nephropathy. Acute tubular necrosis and borderline rejection showed 25 and 50% C4d positivity, respectively. Amongst various histological features, capillary margination of polymorphs and dilatation of peritubular capillaries (PTC-D) showed significant association with C4d positivity (P < 0.005). In cases of CAN, transplant glomerulopathy had significant association with C4d positivity. C4d-positive cases had a higher mean value of serum creatinine at the time of biopsies. CONCLUSION: It is concluded that C4d staining is a useful adjunct marker of the humoral limb of rejection, both in early and late post-transplant periods.     

Effect of histological damage on long-term kidney transplant outcome

BACKGROUND: Chronic renal allograft failure remains a major challenge to overcome. Factors such as donor quality, delayed graft function (DGF), acute rejection, and immunosuppression are known to affect long-term outcome, but their relationship to histological damage to graft outcome is unclear. METHODS: Protocol kidney biopsies (n=112) obtained at 3 months after transplantation yielded 102 with adequate tissue. Histology was scored by the Banff schema, and compared with implantation biopsies (n=91), repeat 12-month histology (n=39), decline in serum creatinine and serial isotopic glomerular filtration rate, onset of chronic allograft nephropathy (CAN), and actuarial graft survival censored for death with a functioning graft. RESULTS: At a median follow-up of 9.3 years, 20 patients had graft failure and 26 died with a functioning graft. Banff chronic nephropathy was present in 24% of 3-month biopsies, and was predicted by microvascular disease in the donor, cold ischemia, DGF, and acute vascular rejection (P<0.001). Acute glomerulitis at 3 months correlated with segmental glomerulosclerosis at 12 months, subsequent recurrent glomerulonephritis, and graft failure (P<0.01). Subclinical rejection at 3 months occurred in 29% of biopsies, correlated with prior acute rejection and HLA mismatch, and led to chronic histological damage by 12 months (r=0.25-0.67, P<0.05-0.001). Subclinical rejection, arteriolar hyalinosis, and tubulitis present at 3 months had resolved by 12 months. The 10-year survival rates for Banff chronic nephropathy were 90.4% for grade 0, 81.0% grade 1, and 57.9% for grades 2 or greater (P<0.01). Early tubulointerstitial damage at 3 months profoundly influenced graft survival beyond 10 years. CAN was predicted by kidney ischemia, 3-month chronic intimal vascular thickening, tubular injury, proteinuria, and late rejection. Chronic fibrointimal thickening of the small arteries and chronic interstitial fibrosis at 3 months independently predicted graft loss and decline in renal function (P<0.05-0.001). CONCLUSIONS: Early transplant damage occurs in the tubulointerstitial compartment from preexisting donor kidney injury and discrete events such as vascular rejection and DGF. Subsequent chronic damage and graft failure reflect accumulated previous injury and chronic interstitial fibrosis, vascular impairment, subclinical rejection, and injury from late rejection. CAN may be conceptualized as the sequelae of incremental and cumulative damage to the transplanted kidney. The duration of graft survival is dependent and predicted by the quality of the transplanted donor kidney combined with the intensity, frequency, and irreversibility of these damaging insults.     

移植肾的病理类型与肾功能及预后的关系——单中心十年经验回顾分析

目的 分析肾移植受者移植肾的病理类型和特征,及其与肾功能和预后的关系.方法 肾移植术后230例受者接受了移植肾穿刺病理活检,分析其病理表现类型和特征,比较不同病理类型和特征受者移植肾穿刺活检时的血肌酐(SCr)水平,随访受者穿刺活检后1年的移植肾功能情况,评价不同病理特征受者的预后.结果 移植术后3个月时接受了程序性肾活检的10例受者中,9例为正常肾组织,1例为移植后IgA肾病.有肾功能损害临床表现的220例受者中,病理表现为交界性改变33例,急性排斥反应(AR)45例,慢性排斥反应(CR)24例,慢性移植肾肾病(CAN)26例,移植后肾炎(PTGN)39例,以上共167例;另外,28例同时有前面两种或两种以上的病理类型表现,还有CNI肾毒性反应8例,BK病毒肾病7例,急性肾小管坏死5例.有5例受者因采集的移植肾组织过少而不能明确诊断.病理诊断为交界性改变、AR、CR、CAN和PTGN的受者,其穿刺活检时的SCr水平分别为(171±17)、(259±25)、(343±33)、(406±67)和(207±26)μmol/L,不同病理类型者的SCr水平两两比较,差异均有统计学意义(P＜0.01).穿刺活检后1年,随访到上述5种病理类型167例受者中的134例(80.2%),其中交界性改变23例、AR 36例、CR 20例、CAN 18例及PTGN37例,分别有1例(3.1%)、8例(18.2%)、8例(22.2%)、6例(33.3%)、5例(13.5%)发生移植肾功能丧失.穿刺活检后1年,上述5种病理类型移植肾功能异常受者的SCr水平与穿刺时SCr水平的差值(△SCr)分别为(-47±20.7)、(-37.3±36.9)、(25.5±24.3)、(13.5±27.7)和(25.2±17.1)μmol/L.结论 移植肾的病理改变复杂多样,结合移植肾穿刺病理活检结果和临床分析进行准确诊断,可以帮助临床选择合适的治疗方案,促进移植肾的长期存活.     

Immunohistologic analysis of human renal allograft dysfunction

The value of percutaneous core needle biopsy in the immunohistological evaluation of renal allograft dysfunction was studied in 72 consecutive biopsies performed in 42 patients. The phenotypes of infiltrating cells mediating graft destruction were identified with monoclonal antibodies and immunoperoxidase staining techniques. Light microscopy, electron microscopy, and immunofluorescence staining were performed in all biopsies. Biopsies were divided into groups depending on their classification on the basis of standard histologic criteria, i.e., acute tubular necrosis (ATN), acute interstitial rejection, acute vascular rejection, chronic rejection and renal disease in native kidneys (RDNK) of nontransplant patients. Immunohistologic analysis of graft biopsies showed a significant increase in Leu 1 (pan-T cells), (P less than 0.001), Leu 2 (cytotoxic/suppressor cells) (P less than 0.001), and Leu 3 cells (P less than .05) in acute interstitial rejection. The expression of DR antigen was significantly increased in both acute (P less than .025) and chronic (P less than .05) rejection, when compared with the findings in ATN biopsies. Leu M1 (monocytes/activated T cells) and Leu 10 (B cells/macrophages) were significantly increased (P less than 0.05 and P less than .005, respectively) in acute interstitial rejection only. The helper/suppressor ratio of infiltrating cells showed no significant change in any clinopathologic category. There was no correlation between the cell populations infiltrating the graft and those monitored in the peripheral blood. Allograft mononuclear cell infiltrates in cyclosporine (CsA) vs. azathioprine-treated patients revealed significantly fewer Leu 2 (P less than .05) and Leu M1 (P less than .05) cell populations in CsA patients during acute rejection. In 32 of these 72 biopsies (44.4%), the biopsy results provided a direct contraindication to the use of steroids, by allowing differentiation between allograft rejection and other causes of graft dysfunction. A total of 38% of the biopsies yielded a histological diagnosis that contradicted the clinical pre-biopsy diagnosis. All allografts showing evidence of severe small vessel disease and/or antibody-mediated rejection eventually were lost. These data highlight the usefulness of needle biopsy material as a guide to the study of intragraft immune events and to clinical management of recipients.     

移植肾活检病理和治疗效果117例分析

目的 总结本中心移植肾活检的病理学类型、特点和治疗效果.方法 回顾性分析本院2004年2月～2007年11月共117 例移植肾穿刺活检的病理学资料.根据Banff97 移植肾活检病理学诊断与分类方案,结合患者的病史和临床表现制定相应的治疗策略,并对治疗效果进行随访研究.结果 117例移植肾穿刺活检标本的病理类型为:急性排斥反应共68 例,占58.1%;慢性移植物肾病20 例(17.1%);临界性病变11例(9.4%);CNI药物中毒4例(3.4%);急性肾小管坏死3例(2.6%);其他包括正常和无法确 诊共11例(9.4%).经治疗后,急性肾小管坏死和药物中毒的患者全部好转.11 例临界性病变的患者,治疗有效率为81.8%.慢性移植物肾病的20 例患者,治疗后15 理例(75%)好转.三个时间段急性排斥(O～3 个月、3～12 个月和大于12 个月)的治疗有效率分别为57.1%、41.7%和75%.结论 移植肾穿刺活检为临床治疗提供了可靠的依据.急性排斥仍然是影响移植肾功能的重要因素,并且不同时间段发生的急性排斥治疗效果存在差异.提高对临界性病变的认识并早期治疗可以达到很好的效果.