肾移植术后早期排斥反应的处理

目的：探讨。肾移植术后早期排斥反应(AR)的处理方法。方法：对14例。肾移植术后3周内发生AR的患者,应用甲基泼尼松龙(MP)治疗7例,改硫唑嘌呤(Aza)为霉酚酸脂(MMF?)治疗5例,抗CD3治疗6例。结果：应用MP治疗的7例中5例AR逆转,2例无效;改Aza为MMF治疗的5例3例逆转,2例无效(其中包括MP无效的2例改Aza为MMF治疗后1例逆转1例无效)。抗CD3治疗6例4例逆转,2例无效(其中MP治疗无效改Aza为MMF治疗后仍无效的1例逆转,MP治疗无效的基础免疫为CsA加MMF?加Pred的1例无效)。结论：MP可使大部分术后早期AR逆转。应用Aza的患者改用MMP后可使早期AR逆转,MP不能完全逆转的AR改用MMF后也有良好的效果。及时应用抗CD3几乎可使术后早期AR全部逆转。     

Steroid-resistant acute allograft rejection in renal transplantation

Steroid-resistant rejection after pediatric renal transplantation forms a rare but severe complication with a guarded prognosis particularly if this occurs late after transplantation. There is a paucity of data on how to manage these challenging rejection episodes, particularly in the pediatric literature. Mohan Shenoy et al. published a case series of 15 patients who were treated with anti-thymocyte globulin for steroid-resistant acute allograft rejection over a 15-year period in a single center in this issue of Pediatric Nephrology. While the results for the early rejection group were encouraging, the results in the eight patients with late rejection episodes after transplantation were unfavorable and afflicted with a high incidence of side-effects. Important diagnostic tools such as C4d staining of the renal transplant biopsy and the measurement of donor-specific antibodies were underutilized. The editorial reviews the importance of the differentiation between humoral and cellular rejection and the challenges of treating late antibody-mediated acute rejection in these patients. A multi-center approach is required to establish a registry of these events and ideally prospective randomized interventions should be designed to provide some evidence base for the management of this challenging complication after pediatric renal transplantation.     

Osteopontin expression in acute renal allograft rejection

BACKGROUND: Osteopontin (OPN) is a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney. The role of OPN and its expression in human renal allograft rejection are unknown. METHODS: We examined by immunohistochemistry and in situ hybridization, renal biopsies from patients with acute rejection (N= 22), protocol biopsies without rejection (N= 9), and perioperative donor biopsies (N= 35) for intrarenal expression of OPN, and its correlation with clinical, laboratory, and histopathologic parameters. In the rejection biopsies, interstitial monocyte/macrophage infiltration, tubulointerstitial cell proliferation/regeneration and apoptosis were investigated. RESULTS: In the majority of rejection biopsies, OPN expression by proximal tubular epithelium was widespread, and tended to be enhanced in the tubules surrounded by numerous inflammatory cells. Conversely, in patients that did not experience episodes of rejection and in donor biopsies, OPN expression by proximal tubules was nil or weak. OPN mRNA was colocalized with its translated protein in the renal tubular epithelium. OPN expression positively correlated with the degree of interstitial inflammation (P < 0.05), CD68+ monocyte infiltration (P < 0.01), Ki-67+ regenerating tubular and interstitial cells (P < 0.05 and P < 0.005, respectively), but not with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive apoptotic tubular cells. CONCLUSION: These data suggest that inducible expression of OPN in the tubular epithelium may have a pathogenic role in acute renal allograft rejection by mediating interstitial monocyte infiltration and possibly tubular regeneration.     

移植肾急性排斥反应的免疫表型

目的阐明移植肾急性排斥反应的发生机制。方法发生严重急性排斥反应的１６例移植肾行免疫组化染色,其中６例行免疫胶体金电镜观察。结果移植肾组织中主要免疫活性细胞为Ｔ细胞,动脉壁及肾小管细胞间的Ｔ细胞均为ＣＤ８细胞。结论移植肾急性排斥反应主要是由Ｔ淋巴细胞尤其是ＣＤ８细胞介导的一种免疫损伤。     

移植肾急性排斥反应新认识

急性排斥反应是影响肾移植长期预后的重要因素。在新型免疫抑制剂应用下,急性排斥反应具有表现不典型、难治性排斥反应比例高等特点。本文从发生急性排斥反应高危因素的术前筛查与处理、急性排斥反应早期诊断方法以及对急性排斥反应的干预和免疫抑制药物合理应用、移植后感染预防等方面,综合浙江大学医学院附属第一医院肾脏病中心的临床研究结果,探讨发生急性排斥反应的高危因素、诊断和防控措施,以提高肾移植后长期存活率。     

Plasma cell-rich acute renal allograft rejection.

BACKGROUND: Acute renal allograft rejection is usually seen within the first 3 months posttransplant, and is characterized by an intense infiltrate of T cells. Some acute rejections, however, contain many plasma cells and/or appear late posttransplant. METHODS: We have investigated 27 cases of intensely plasma cell-rich acute rejections (PCAR) from 1987 to 1997 and have compared them to 21 control cases (CAR) of typical acute rejection. Each group was divided into early (<6 months) and late (>6 months) subgroups. PCAR and CAR cases were matched for histological features of chronic allograft nephropathy. In all four groups, most cases had Banff '97 type IB and IIA acute rejection. RESULTS: A significantly greater number of PCAR cases experienced graft failure due to chronic allograft nephropathy or complications of acute rejection (P<0.05). There was no significant difference between PCAR and CAR in HLA matching, occurrence of posttransplant acute tubular necrosis, presence versus absence of previous allografts, number of previous or subsequent acute rejection episodes, Banff '97 sum scores for acute rejection, cyclosporine A or FK506 levels, or percent change from baseline creatinine at time of biopsy. Plasma cells in PCAR cases showed IgG predominance whereas those in CAR had comparable staining for IgG and IgA. Kappa and lambda light chain immunostaining of all PCAR cases revealed polyclonality. Three of 18 PCAR cases studied for the presence of Epstein-Barr virus RNA showed scattered positivity in 2-7% of lymphoid cells, although the remainder was negative. None of the PCAR cases developed post-transpland lymphoproliferative disorder. CONCLUSIONS: We conclude that PCAR can occur from 1 month to many years posttransplant, is associated with poor graft survival, and is not a manifestation of concomitant chronic allograft nephropathy or viral infection, including posttransplant lymphoproliferative disorder.     

肾移植术后急性体液性排斥反应的治疗

目的 总结肾移植术后急性体液性排斥反应中针对HLA抗体的检测和处理经验.方法 肾移植受者15例,术前行HLA分型、交叉配型和群体反应性抗体(PRA)的检测,术后采用他克莫司(或环孢素A)、霉酚酸酯和糖皮质激素预防排斥反应.15例于肾移植后1～14 d发生抗体介导的急性排斥反应(AMR),采用抗胸腺细胞球蛋白(100 mg/d,使用5 d)治疗,或将环孢素A转换为他克莫司,当PRA明显升高,且血清中出现供者特异性HLA抗体时,即行血浆置换(PP),共行1～5次,每次PP后静脉输注免疫球蛋白(IVIG)100～150 mg/kg,最后1次PP后给予WIG 200～500mg/kg.结果 术后出现抗供者特异性HLA Ⅰ类抗体者9例,抗HLAⅡ类抗体者4例,同时出现抗Ⅰ、Ⅱ类抗体者2例.14例的AMR逆转,1例术后发生移植肾功能恢复延迟,彩色多普勒超声波显示移植肾血流灌注差,于术后第10天切除移植肾.并行二行肾移植.2例AMR后并发急性肾小管坏死,透析后移植肾功能恢复正常.抗排斥反应治疗期间患者均未发生严重感染.随访12～52个月,1例因慢性移植肾肾病恢复血液透析治疗,1例死于心血管疾病,其余患者移植肾功能稳定.结论 将ATG、PP和IVIG联合应用能有效逆转AMR.     

Adhesion molecule polymorphisms in acute renal allograft rejection

Acute rejection is the main cause of early renal allograft failure. Adhesion molecules provide signals for activation and recruitment of effector cells leading to graft infiltration by host T cells, which are key to allograft rejection. This study was undertaken to analyze the adhesion molecule gene polymorphisms in renal transplant recipients and to investigate their potential association with the development of acute allograft rejection. A total of 120 renal transplant recipients and 100 controls were retrospectively genotyped. Seven nucleotide polymorphisms in intracellular adhesion molecule (ICAM)-1, platelet endothelial cell adhesion molecule (PECAM)-1, L-selectin, and E-selectin were analyzed using allele-specific polymerase chain reaction (PCR)-SSP assay and PCR-restriction fragment length polymorphism (RFLP). Recipients were selected on the basis of the development of acute allograft rejection in the first 6 months after renal transplantation. Forty-one patients developed acute allograft rejection and 79 showed uneventful courses. There was no evidence for an association of any polymorphism with acute rejection. Thus, we concluded that these genes do not predispose to acute renal allograft rejection.     

Determinants of hypofiltration during acute renal allograft rejection

This study sought to determine the extent to which GFR is decreased during acute renal allograft rejection in human subjects and to determine the mechanism of the decrease in GFR. Eight patients with biopsy-proven acute rejection were compared with 18 recipients of optimally functioning renal allografts. GFR and renal plasma flow (RPF) were measured as the clearance of inulin and para-aminohippuric acid, respectively. Arterial BP was determined, blood was sampled, and plasma oncotic pressure (pi(A)) was measured. Glomeruli obtained by biopsy during rejection were subjected to morphometric analysis, for determination of K(f). Control morphometric values for healthy glomeruli were provided by 10 living donors from whom biopsies were obtained at the time of organ donation. The subjects in the acute rejection group exhibited a significantly reduced GFR of 17 +/- 4 ml/min per 1.73 m(2), compared with 72 +/- 4 ml/min per 1.73 m(2) for control subjects (P < 0.001). With the use of a sensitivity analysis to take into account the unknown para-aminohippuric acid extraction ratio, the RPF rate was calculated to have likely been significantly decreased, by 45 to 70%, in the acute rejection group. Neither the plasma oncotic pressure nor the mean arterial pressure differed between the two groups. Morphometric analysis revealed no difference in the single-nephron K(f) values for the acute rejection group, compared with the control group. These results indicate that acute renal allograft rejection causes a profound decrease in GFR, which is attributable to a decrease in RPF alone or in combination with a decrease in the glomerular transcapillary hydraulic pressure gradient (DeltaP).     

Study of acute antibody-mediated rejection in renal allograft biopsies

INTRODUCTION: Acute B-cell-mediated rejection (AMR) was ill-defined until the 6(th) Banff meeting establishing the criteria. We performed a retrospective analysis of renal allograft biopsies to evaluate immune injury with reference to the Ahmedabad Tolerance Induction Protocols (ATIP). METHODS: We evaluated renal allograft biopsies belonging to 3 groups: group A patients (n = 120) underwent a modified ATIP with addition of mesenchymal stem cells, anti-B-cell antibodies, and higher target-specific irradiation; group B patients (n = 351) belong to the old ATIP; and group C (n = 142) were controls who opted out of ATIP. The majority were biopsied 2 or 3 times. Biopsies were subdivided: 相似文献   

肾移植急性排斥反应中肾小管上皮细胞凋亡的观察

目的 探讨肾移植急性排斥小以细胞凋亡与移植排斥的关系。方法 选用近交系ＤＡ大鼠,ＬＥＷ大鼠进行原位左肾移植。实验组：异基因移植组（ＤＡ－ＬＥＷ）,对照组;基因移植组（ＬＥＷ→ＬＥＷ）。于手术后第２、４、６天分别取移植肾进行病理学检查及电镜扫描,采用ＴｄＴ介导的脱氧核苷酸原位末端标记法（ＴＵＮＥＬ）检测移植肾脏中的凋主血清肌酐水平。结果 病理学检查结果显示实验组大鼠在术后第２、４、６天分别发生轻、中     

RS-61443 reverses acute renal allograft rejection in dogs

RS-61443 is a noncompetitive allosteric inhibitor of inosine monophosphate dehydrogenase. At blocks the proliferative response of T and B lymphocytes, prevents the generation of cytotoxic T cells, and inhibits antibody formation. This study was conducted to see whether or not RS-61443 can reverse acute renal allograft rejection in dogs. At was possible to reverse this process.     

Urinary secretory immunoglobulin A in acute renal allograft rejection

Periodical determinations of the urinary secretory immunoglobulin A (S-IgA) excretion rate were performed in 12 cadaveric graft recipients. In five patients with primary functioning grafts the S-IgA excretion on the first postoperative day was 4.2 +/- 2.6 mg/g creatinine, decreasing to 1.8 +/- 1.2 mg/g creatinine (P less than 0.05) at the day of discharge. Acute tubular necrosis developed in the seven remaining patients. In this group the initial S-IgA excretion was 12.6 +/- 7.5 mg/g creatinine (P less than 0.05 compared to the former group), decreasing to 2.0 +/- 0.9 mg/g creatinine (P less than 0.05) at discharge. An acute rejection episode was observed in six patients. The S-IgA excretion increased from 3.0 +/- 1.5 mg/g creatinine 3-4 days before rejection to 6.4 +/- 3.1 mg/g creatinine (P less than 0.05) 1-2 days before rejection, and peaked at 14.0 +/- 8.6 mg/g creatinine (P less than 0.05) when the diagnosis of rejection was established and anti-rejection treatment was started. In three patients the initial steroid pulse therapy was not successful and S-IgA excretion further increased to 29.0 +/- 15.6 mg/g creatinine. After successful anti-rejection treatment, using steroids and OKT3, the S-IgA excretion decreased to 3.4 +/- 2.6 mg/g creatinine. In acute graft rejection, the elevated globulin synthesis by infiltrating plasma cells. In the early phase of rejection, dimeric IgA is the only immunoglobulin able to penetrate into the urine by transepithelial transport after binding to secretory component expressed on tubular epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double-blind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection

BACKGROUND: Renal transplant recipients experience adverse events attributed to corticosteroid therapy. METHODS: This was a multicenter, randomized, double-blind, 6-month, controlled steroid dose-reduction study in renal transplant recipients with an unblinded 6-month follow-up. In the low/stop arm, corticoste. roids were given at half the dosage of control for 3 months from the date of transplantation, and then withdrawn. Both arms received mycophenolate mofetil and cyclosporine. The primary endpoint was the incidence of biopsy-proven acute rejection at 6 months posttransplantation. RESULTS: There were 248 patients in the control group and 252 in the low/stop group. At 6 months the low/stop group had more biopsy-proven acute rejection episodes than the control (23% vs. 14%; P=0.008). At 12 months this increased to 25% vs. 15%. Most rejections were Banff grade I. Twelve-month graft loss was 5% in the low/stop group vs. 4% in the control. At 6 and 12 months serum cholesterol (P<0.01, P<0.01), triglycer. ides (P<0.01, P<0.01), and systolic blood pressure (P<0.001, P<0.001) were lower in the low/stop group. Diastolic pressure was lower (P<0.01) and lumbar spine bone density was greater (P<0.01) in the low/ stop group at 12 months. CONCLUSIONS: In renal transplant recipients treated with mycophenolate mofetil and cyclosporine, reduction and early withdrawal of the prophylactic corticosteroid dose is feasible without an unacceptable increase in serious rejection episodes. This is accompanied by a significant reduction of steroid-related adverse events.     

预防预致敏受者尸体肾移植术后急性排斥反应的临床研究

目的 探讨HLA配型及新型免疫抑制剂治疗方案对预防致敏患者肾移植术后急性排斥反应的影响.方法 实验组选择46例术前致敏患者(术前PRA>10%),对照组选择同期705例未致敏患者(术前PRA<10%),实验组患者均采用诱导治疗(ATG 100 mg/d,5～7 d)+三联免疫抑制剂维持治疗方案(FK506+MMF+激素),比较两组间患者术后急性排斥反应发病率、移植肾功能延迟恢复比例、移植肾/患者一年存活率,同时分析HLA配型对移植肾急性排斥反应的影响.结果 实验组与对照组急性排斥反应的发病率分别为30.43%和19.57%(P<0.05);移植肾功能延迟恢复发病率分别为60.86%和11.87%(P<0.01).患者一年存活率分别为95.65%和98.44%,一年移植肾存活率分别为93.48%和96.88%;一年时平均血肌肝分别为130 mmol/dL和125 mmol/dL,差异无统计学意义.实验组患者HLA相配率(4.2)明显高于对照组患者(2.8)(P<0.05).实验组中HLA配型2-4错配的患者与0-2错配患者的急性排斥反应发病率有显著性差异,高度致敏患者(移植术前PRA>50%)急性排斥反应发病率较低度致敏患者(PRA 10%～20%)发病率高,移植术后PRA水平持续升高者更容易出现急性排斥反应.结论供、受者之间良好的HLA配型及采用新型免疫抑制药物治疗方案,对预防及减轻致敏患者移植术后急性排斥反应疗效确切.     

OKT3治疗移植肾难治性排斥反应

为了解ＯＫＴ３对移植肾难治性排斥反应的治疗效果，１９９３年１月至１９９６年６月，我们对４４例肾移植术后移植肾难治性排斥反应（其中加速性排斥反应７例，急性排斥反应３７例）应用ＯＫＴ３治疗。结果：６例加速性排斥反应及３１例急性排斥反应逆转，总逆转率为８４．６％。２５例对ＯＫＴ３治疗产生迅速反应，平均逆转时间为７±４天，１２例发生延迟性反应，平均逆转时间为３４±３天（Ｐ＜０．０１）。作者认为：ＯＫＴ３治疗难治性排斥反应效果显著。巨细胞病毒感染及细胞因子释放综合征是ＯＫＴ３治疗的主要副作用。患者对ＯＫＴ３治疗的延迟性反应与细胞因子释放综合征及排斥损害有关。产生低滴度抗ＯＫＴ３抗体的患者可再次接受ＯＫＴ３治疗。