Rituximab induction therapy in highly sensitized kidney transplant recipients

Background  The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients.

Methods  Seven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21–47 years). The duration of hemodialysis was 3–12 months, with a mean duration of 11 months. For 4 patients, this was the second transplant; the previous graft survival time was 2–11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25–37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg∙kg^-1∙d^-1) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m²) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery. Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored.

Results  No patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post-surgery. Diagnosis of acute rejections was based on the clinical assessments and pathological biopsy results. According to the Banff 07 classification of renal allograft pathology, one of the patients was Ia and the other was IIa; the C4d staining was negative in both patients. One patient received methylprednisolone plus cyclophosphamide and the other received antithymocyte globulin (ATG) therapy, both leading to successful reversion of the acute rejection. All patients were discharged postoperatively and all had normal renal function during the 7th to 12th month follow-up. Pulmonary infection occurred in 1 patient 4 months after surgery and was successfully cured.

Conclusion  Rituximab induction therapy can reduce the occurrence of postoperative humoral rejection in highly sensitized renal transplant recipients, suggesting that kidney transplantation may be safe and effective for these patients.

     

Protein A immunoadsorption combined with rituximab in highly sensitized kidney transplant recipients

Background The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of protein A immunoadsorption combined with rituximab （RTX） in highly sensitized recipients of kidney transplants.
Methods Seven highly sensitized recipients of living-related renal transplants （4 men and 3 women, mean aged 42.5 years old （range 33-51）） were pretreated with this combination. Human leukocyte antigen （HLA） mismatch number was 2-5. Panel reactive antibody （PRA） of class Ⅰwas high in 2 cases and that of class Ⅱwas high in 1 case. All patients were pretreated with immunoadsorption 2-10 times. Immunoglobulin and PRA changes were monitored before and after absorption. The operation was conducted when PRA or immunoglobulin levels were at or below normal levels. Immunosuppressive drugs were provided 3-5 days before the operation, and one dose of RTX （375 mg/m^2） was infused with polyclonal antibody on the day of operation. Postoperative creatinine （Cr）, creatinine clearance rate （Ccr）, PRA ratio, and immunoglobulin changes were monitored.
Results All 7 patients had good recovery without delayed graft function. Acute rejection occurred in 3 cases at postoperative days 8, 10, and 14, respectively. The Banff 07 biopsy grades were la in 1 case and lla C4d0 in 2 cases. Successful reversion was achieved after giving methylprednisolone or antithymocyte immunoglobulin ＋ cyclophosphamide. All patients were discharged with normal renal function, mean class Ⅰ PRA was 14% and mean class ⅡPRA was 35%. PRA was completely negative in 3 cases.
Conclusion Protein A immunoadsorption combined with RTX can safely reduce the occurrence of humoral rejection in highly sensitized renal transplant recipients.     

Preoperative single-bolus high-dose antithymocyte globulin as induction therapy in sensitized renal transplant recipients

Background Immunological sensitization remains a major problem following renal transplantation. There is no consensus for the management of sensitized renal allograft recipients. The patients become tethered to dialysis while waiting for compatible donors. This study was designed to evaluate the efficacy and safety of preoperative single- bolus high-dose antithymocyte globulin (ATG) as induction therapy in sensitized renal transplant recipients.Methods A total of 56 patients were divided into two groups according to the level of panel reactive antibody (PRA): non-sensitized group (PRA<10%, n=30) and sensitized group (PRA≥10%, n=26). The characteristics of the recipients and donors were comparable between the two groups. Mycophenolate mofetil (MMF, 1 g) or ATG (iv. 9 mg/kg) were given preoperatively in the two groups as induction therapy. After the transplantation, the patients were treated with standard triple therapy regimen consisting of tacrolimus (FK-506) or cyclosporine A, MMF, and prednisolone. Acute rejection (AR) and infection episodes were recorded and renal function was monitored during a 12-month follow-up. χ(2) test and t test were used to analyze the data.Results During the follow-up, 6 patients (20.0%) suffered AR episodes in the non-sensitized group and 4 (15.4%) in the sensitized group (P=0.737); 8 patients (26.7%) experienced 11 infection episodes (average, 1.4 episodes per infected patient) in the non-sensitized group, and 6 (23.1%) experienced 10 infection episodes (average, 1.7 episodes per infected patient) in the sensitized group (P=0.757, 0.890). The safety of the drugs, which was assessed by the occurrence of side effects, was comparable between the two groups. The hospital stay was 13－25 days (mean, 16.7±3.3) in the non-sensitized group and 14－29 days (mean, 16.2±3.1) in the sensitized group, respectively (P=0.563). No delayed graft function (DGF) was observed in all the patients. Both the 12-month actuarial patient and graft survival rates were 100% in the two groups.Conclusion Preoperative single-bolus high-dose ATG is an effective and safe induction therapy yielding acceptable acute rejection rate in sensitized renal transplant recipients.     

PRA配型技术在致敏受者肾移植术中的应用研究

目的 探讨群体反应性抗体(PRA)配型技术在致敏受者肾移植中的临床效果.方法 应用抗原板(LAT),采用酶联免疫吸附法(ELISA)检测肾移植受者术前的PRA;采用PRA配型技术进行术前配型.结果 12例致敏受者组采用PRA配型技术,肾移植术后肾功能恢复正常,无1例发生超急性排斥反应,术后1个月内急性排斥反应的发生率为25%;同期43例非致敏受者组,术后1个月内急性排斥反应的发生率为18.6%,虽较致敏受者组低,但两组之间差异无统计学意义.结论 PRA配型技术对减少致敏受者肾移植排斥反应,提高移植物存活率具有重要意义.     

Alemtuzumab induction therapy in highly sensitized kidney transplant recipients

Background  Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.

Methods  In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody >20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given. The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF). Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. χ² test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.

Results  Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P >0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P <0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P >0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P >0.05).

Conclusion  Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.

     

免疫吸附在高致敏肾移植受者中的应用

目的 探讨蛋白A免疫吸附(IA)治疗在预防高致敏肾移植受者急性排斥反应中的效果和安全性.方法 回顾性分析2008年3月至2009年10月首都医科大学附属北京朝阳医院收治的12例群体反应性抗体(PRA)高的肾移植患者在术前应用IA治疗的临床资料.比较治疗前后血免疫球蛋白IgG、IgM、IgA及PRA水平.观察患者术后急性排斥反应发生情况及不良反应.结果 12例患者IA治疗次数为3～8次.治疗后PRA Ⅰ和Ⅱ类抗体均较治疗前明显下降[14%(4%,27%)比86%(73%,98%),6%(0,23%)比68%(34%,88%),均P＜0.01];血清总IgG水平较治疗前明显下降[(550±341)g/L比(1301±393)g/L,P＜0.01];IgA和IgM也较治疗前降低[(144±78)g/L比(185±93)g/L,(103±48)g/L比(131±66)g/L,P＜0.01].5例患者在术后发生了急性排斥反应,给予抗胸腺细胞球蛋白(ATG)或联合IA(2例)治疗后均逆转.术后6个月内,1例患者发生烟曲霉菌肺炎,2例出现卡氏肺囊虫肺炎,均治愈.结论 IA治疗可降低高致敏患者体内预存抗体水平.辅以诱导治疗对预防和减轻肾移植术后排斥反应疗效确切.     

供体脾灌注对高度致敏肾移植受者嵌合体形成的影响

目的探讨供体脾灌注对高度致敏肾移植受者稳定期嵌合体形成及移植肾功能的影响。方法对16例高度致敏患者进行配对分组，实验组肾移植术中先予供体脾灌注40min，前瞻性观察脾灌注对患者术后6个月内嵌合体形成、移植肾排斥反应发生及移植肾功能的变化。结果脾灌注后受者外周血中供者来源的有核细胞数量显著增加，受者形成稳定嵌合体的时间较早，例数比对照组更多；肾移植术后脾灌注组排斥反应发生时间较对照组延迟，排斥反应严重程度明显较对照组轻微；术后6个月时，脾灌注组患者血肌酐值低于对照组。结论供体脾灌注可以显著提高高敏肾移植受者外周血中供者来源的有核细胞数量，减轻排斥反应强度，从而促进受者嵌合体的形成，有利于改善稳定期移植肾功能。     

影响致敏患者移植肾存活的危险因素分析

目的探讨影响致敏患者移植肾存活的危险因素,识别引起移植物失功的高危患者,以提高致敏患者移植肾长期存活率。方法选择102例行肾移植术的致敏患者进行回顾性研究,用Kaplan-Meier计算1、3、5年移植肾存活率,用log-rank进行单因素分析和Cox模型多因素回归分析,计算相对危险度。结果102例致敏患者随访期间移植肾失功16例,其中死亡7例,术后1年内死亡5例,术后2及3年带肾死亡各1例。死亡原因肺部感染5例、心血管疾病2例,失访3例。1、3、5年人存活率为95%、93%和93%,1、3、5年肾存活率为90%、85%和75%,移植肾半生存期为8.9年。单因素及多因素分析表明受者年龄、移植次数、PRA水平、术后PRA水平升高、HLA相配程度、移植肾功能恢复正常时间、移植肾功能延迟恢复、急性排斥反应、血肌酐水平、感染等10个因素对移植肾的存活产生重要或非常重要影响。结论通过控制影响移植肾存活的危险因素,致敏患者移植肾存活同样能取得满意效果。     

Risk factors for graft survival in sensitized recipients of kidney transplantation.

OBJECTIVE: To investigate the independent prognostic factors for graft survival in sensitized recipients undergoing kidney transplantation, so as to identify the individuals at high risk of graft loss before transplantation. METHODS: A retrospective investigation was conducted in 102 sensitized kidney transplant recipients and 31 relative variables were analyzed with SPSS10.0 software. Using log-rank method, the influence of these variables on short- and long-term graft survivals was evaluated, and Kaplan-Meier analysis was performed to estimate the 1-, 3- and 5-year graft survival rates and half-life. Proportional hazards regression analysis (Cox model) was used to assess the relative risks of the potential variables. RESULTS: In the recipients with a mean half-life of 8.9 years, the 1-, 3- and 5-year graft survival rates were 90%, 85%, and 75%, respectively. By log-rank analysis, the factors affecting short- and long-term graft survivals were identified, namely the recipient age, times of transplantation, levels of panel reactive antibody and the post-operative anti-HLA-IgG antibody, HLA mismatch, renal function, time needing for graft function recovery, presence of acute rejection, delay of graft function recovery and infection, which affected the graft survival demonstrated by Cox model multivariate analysis. CONCLUSION: High-quality donor kidney and minimization of the risk factors for graft survival may insure successful kidney transplantation in sensitized recipients.     

2剂赛尼哌预防肾移植术后急性排斥反应的应用研究

目的 :探讨赛尼哌在预防同种肾异体移植术后急性排斥反应的作用。方法 :回顾分析了已随访 1年的 32例应用 2剂赛尼哌患者的临床效果 ,并以同期肾移植 92例作为对照组。结果 :赛尼哌组在 3月内急性排斥反应发生率 (3.1% )显著低于对照组 (2 3.9% ) (P <0 .0 5 ) ,在感染及副作用方面与对照组无显著性差异。结论 :2剂赛尼哌加上CsA ,MMP ,Pred联合应用的免疫抑制方案对预防同种尸体肾移植受者的急性排斥反应的发生是安全有效的。     

Expression characteristics of major histocompatibility complex class I-related chain A antibodies and immunoadsorption effect in sensitized recipients of kidney transplantation

Background  Sensitized recipients have a high risk of immunological graft loss due to hyperacute rejection and/or accelerated acute rejection. The presence of major histocompatibility complex class I-related chain A (MICA) antibodies has also been described associated with an increased rate of kidney-allograft rejection. The aim of this study was to describe the expression of MICA antibodies in sensitized recipients of renal transplantation and evaluate its influence on the kidney transplantation recipients.

Methods  A total of 29 sensitized recipients were included in this study. All patients received the MICA antibodies detection before and after protein A immunoadsorption. Panel reactive antibody (PRA), HLA-matches, acute rejection and postoperative one to four-week serum creatinine level were also collected and analyzed, respectively. No prisoners were used in this study.

Results  Eight patients (27.6%) in all 29 sensitized recipients expressed the MICA antibodies but did not show higher acute rejection rate than the non-expressed patients (3/8, 37.5% vs. 8/21, 38.1%; P=1.000). Recipients with PRA >40% showed higher expression levels of MICA antibodies than the recipients with PRA <40% (7/16, 43.8% vs. 1/13, 8.3%; P=0.044). HLA mismatch did not have any effect on the expression of MICA antibodies (P=1.000). MICA antibodies positive group had higher serum creatinine level than the control in postoperative one week ((135.4±21.4) µmol/L vs. (108.6±31.6) µmol/L, P=0.036), but no significant difference in postoperative four weeks ((89.0±17.1) µmol/L vs. (77.1±15.9) µmol/L, P=0.089). MICA antibodies decreased significantly after protein A immunoadsorption.

Conclusions  MICA antibodies increase in the sensitized recipients, which have significant effects on the function of allograft in early postoperative period. Protein A immunoadsorption can decrease MICA antibodies effectively in sensitized recipients.

     

群体反应性抗体对肾移植后人/肾存活率影响的临床分析

目的回顾性调查群体反应性抗体(PRA)对肾移植术后1、3、5年人/肾存活率的影响。方法纳入北京军区第二八一医院2000年1月~2012年3月肾移植受者469例,采用酶联免疫吸附法(ELISA)检测受者移植前PRA水平,以PRA≤10%为阴性结果,10%40%为高度致敏,并对1、3、5年人/肾存活率进行统计。结果 469例肾移植受者中,PRA阴性349例(阴性组),PRA阳性120例(阳性组),其中Ⅰ类抗体阳性66例,Ⅱ类抗体阳性31例,23例同时存在Ⅰ类和Ⅱ类抗体。术前PRA阴性组与阳性组1、3、5年人存活率分别为98.3%、90.9%、80.7%和93.3%、82.9%、62.9%;1、3、5年肾存活率分别为96.8%、87.9%、75.9%和86.7%、76.1%、50.5%,二组相比1、3、5年人/肾存活率均差异有统计学意义(P<0.05),轻度致敏组的1、3、5年人存活率、肾存活率与PRA阴性组相比,差异无统计学意义(P>0.05);中度致敏组的1、3、5年人/肾存活率与阴性组比较,差异有统计学意义(P<0.05);高度致敏组的1、3、5年人/肾存活率与阴性组比较,差异有统计学意义(P<0.05)。结论 PRA是肾脏移植术前筛选致敏受者的重要指标,PRA阳性会影响移植物的长期存活,PRA阳性患者在肾移植手术前必须进行严格的组织配型,采取措施降低抗体水平,选择合适的供体与手术时机,以提高人/肾存活率。     

Current trend of induction and maintenance treatment in positive panel-reactive antibody patients: a report on OPTN/UNOS kidney transplant registry data

Background  The status of sensitization in kidney transplant recipients in the last 10 years and the trend of induction and maintenance therapy in patients of different panel-reactive antibody (PRA) levels have not been analyzed. The aim of this study was to investigate the current status of pre-transplant sensitization and its association with graft outcome.

Methods  A total of 155 570 kidney transplants reported to United Network for Organ Sharing (UNOS) during 2000–2009 were included in this study. We investigated the current status of pre-transplant sensitization and its association with graft outcome, and also compared the usage trend of 16 induction agents and 7 maintenance immunosuppressants in patients at different PRA levels. The difference of distributions of categorical variables between groups was investigated using the chi-square test. Unpaired t test or one-way analysis of variance (ANOVA) were used for numerical variables. The survival rates of transplant recipients were estimated using Kaplan-Meier methods and significance was determined by Log-rank test. Two-side P value <0.05 was considered statistically significant. All statistical analyses were performed using STATA 10 with all available updates as of March 2010 (StataCorp LP, College Station, Texas 77845, USA).

Results  Despite the fact of the decreased percentages of kidney transplant recipients with presensitization history, the mean PRA levels of all kidney recipients has been increasing in the last 7 years, which was possibly due to the introduction of more sensitive antibody testing techniques. The percentage of patients with treated rejection episodes within one year post-transplant were significantly higher in sensitized patients (PRA=50%–100%:14.3% and PRA= 1%–49%:13.9%) than in non-sensitized patients (12.4%). Both 1- and 5-year graft survival rates improved in the last 10 years; this was more significant in high PRA patients. Thymoglobulin was the most commonly used induction agent in last 10 years. Its users increased from 10% to 46% in non-sensitized patients, from 12% to 57% in PRA 1%–49% patients, and from 19% to 63% in PRA 50%–100% patients. The users of Campath, intravenous immunoglobulin (IVIG), and Rituximab have been increasing and reached 16%, 20%, and 11% in highly sensitized patients. In the last 5 years, steroid-free patients were 33%–36%, 30%–37%, and 10%–25% for PRA 0, 1%–49%, and 50%–100% respectively. Almost 90% of patients were on Prograf at discharge. It seems that Myfortic users have been increasing since 2005 and it may soon replace mycophenolate mofetil (MMF) if long-term follow-up study conforms its safety and efficacy.

Conclusions  Application of sensitive antibody testing techniques increased the mean PRA levels of transplant recipients in spite of a decreased percentage of sensitized recipients. Induction and maintenance therapy differed in patients at different PRA levels.

     

早期低剂量利妥昔单抗在ABO血型不相容肾移植中的应用

目的 探讨不同方案利妥昔单抗在ABO血型不相容肾移植(ABOi-KT)中应用的利弊,总结合理利用利妥昔单抗使用方案.方法 33例ABOi-KT受者,术前均使用MMF+FK506等10~14 d,配合血浆置换和血浆双重滤过.利妥昔单抗的使用有如下4个不同方案:方案一,术前24 h内单次使用利妥昔单抗500 mg;方案二,术前1周和术前24 h内各使用利妥昔单抗500 mg;方案三,术前2周、术前1周和术前24 h内分别使用利妥昔单抗200、200、500 mg;方案四:术前2周、术前1周和术前24 h内分别使用利妥昔单抗200、200、100 mg.监测4组患者不同时间点血型抗体滴度.统计各组血浆处理次数、使用血浆量,比较不同组别对比术后人肾脏存活率、1年内的感染发生率.结果 除方案二中1例出现急性排斥反应,行移植肾切除外,余32例ABOi-KT均取得成功,未出现大出血和肾功能延迟恢复.方案一配合血浆置换和血浆双重滤过次数最多,使用血液制品也最多,方案三和四最少;方案三和四中术后2周内血型抗体滴度反弹较其他方案慢.结论 (1)联合应用免疫抑制剂、血浆置换和(或)双重血浆置换、利妥昔单抗等方法处理ABOi-KT受者是安全有效的;(2)早期低剂量使用利妥昔单抗方案(方案四)是安全有效的,同时可以减少移植受者血浆处理次数,减少术后血型抗体反弹概率,减少手术费用.     

Immunosuppression induction with daclizumab and antithymocyte globulin in cardiac transplantation: clinical experience with 8 cases.

OBJECTIVE: To review the clinical experience of immunosuppression induction therapy to prevent acute rejection in 8 patients with cardiac transplant. METHODS: Between June, 2000 and May, 2002, 8 patients with end-stage dilated cardiomyopathy undergoing orthotopic cardiac transplantation received induction therapy with two-dose daclizumab (1.0 mg/kg), given intravenously within 12 h before cardiac-transplantation surgery and two weeks thereafter, and with an initial 5-day course of intravenous antithymocyte globulin (100 mg/d) following transplantation. Cyclosporine or tacrolimus, mycophenolate mofetil or azathioprine, and prednisolone were applied for immunosuppression maintenance. RESULTS: No death occurred during the follow-up. Routine endomyocardial biopsies in all cases performed in the early stage detected only mild rejection, and no acute allograft or renal dysfunction was found. Three patients developed opportunistic infection, and only one had late acute rejection in the 14th post-transplantation month. CONCLUSIONS: Induction therapy with intravenous daclizumab and antithymocyte globulin is effective to prevent acute rejection and alleviate organ dysfunction in cardiac transplantation, but might increase the chance of infections.     

Impact of human leukocyte antigen matching and recipients′ panel reactive antibodies on two-year outcome in presensitized renal allograft recipients

Background Renal transplantation in sensitized candidates remains a highly significant challenge worldwide. The production of panel reactive antibody （PRA） against human leukocyte antigen （HLA） is a major risk factor in presensitized recipients. The aim of this study was to evaluate the impact of HLA matching and recipients＇ PRA on two-year outcome in presensitized renal allograft recipients.
Methods We determined the percentage of panel reactivity and specificity of anti-HLA immunoglobulin （Ig） G antibodies in 73 presensitized renal allograft recipients compared with 81 unsensitized recipients （control group）. HLA genotyping of both recipients and corresponding donors was performed by PCR with sequence-specific primers （PCR-SSP）. We analyzed the factors influencing the early graft outcome （two-year rejection rates and survival rates of the grafts）, including HLA mismatching, class and degree of panel reactivity, and target antigen of donors.
Results Presensitized recipients had a worse two-year outcome than unsensitized recipients （P=0.019 for rejection rate, P=0.01 for survival rate）. The difference in number of HLA-mismatched alleles with either 6-antigen matching （Ag M） standard or amino acid residue matching （Res M） standard was not significant between the rejection and non-rejection groups of presensitized recipients or between the graft survival group and graft loss group. Compared with the control group, recipients with both PRA-I and PRA-II antibodies had a significantly worse two-year outcome （P=0.001 for rejection rate, P=0.002 for survival rate）. The two-year outcomes of the peak PRA 〉50% group and its subgroup, at-transplant PRA 〉50% group, were significantly worse compared with the control group （P=0.025 and P=0.001 for rejection rate, P=0.043 and P=0.024 for survival rate）. The rejection rates of the at-transplant target antigen positive group and its subgroup, HLA-I target antigen positive group, were significantly higher than the control group （P=0.001 and P=-0.001）, target antigen negative group （P=0.003 and P=0.001）, and peak target antigen positive with negative at-transplant target antigen group （P=0.024 and ,0=-0.002）. Two-year graft survival rates of the target antigen positive group and HLA-I target antigen positive group were significantly lower than the control group （P=0.012 and ,P=0.001）. The two-year outcome of target antigen unknown group was similar to that of the target antigen positive group. Presensitized recipients with pre-transplant plasmapheresis or immunoadsorption （PRA prepared group） had a better but non-significant two-year outcome than the control group. However, the PRA unprepared presensitized recipients were different to the control group （P=-0.004 for rejection rate and P=-0.005 for survival rate）. Hyperacute rejection （HR） occurred in three recipients with positive HLA-I target antigen and without mismatch according to Res M and in one case with positive PRA-II （for an unknown target antigen）. No HR occurred in eight cases with positive HLA-II target antigens.
Conclusions Pre-transplant PRA preparations might improve the access of presensitized patients to renal donors. Avoiding antigen-positive donors remains a fundamental measure in preventing HR and early rejections.     

Measurement of serum amyloid A protein concentrations as test of renal allograft rejection in patients with initially non-functioning grafts

Serum amyloid A protein concentrations were monitored in 10 renal transplant recipients who required dialysis after transplantation because of an initially non-functioning graft. Fifteen rejection episodes were identified by repeated fine needle aspiration biopsies of the grafts. All rejections were characterised by pronounced increases in serum amyloid A concentrations, the mean peak value being 363 (SE 57) mg/1 as compared with a mean preoperative concentration of 14 (5) mg/1. The rise in concentrations preceded the start of anti-rejection treatment by an average of 2.5 days in eight of the rejection episodes, in five episodes it occurred the same day, and in two episodes it occurred the next day. With exclusion of the predictable surgery induced rise in values, which peaked on the second postoperative day, there were 17 increases in amyloid A concentrations peaking at greater than or equal to 100 mg/1; in two cases they were not related to documented rejection. These findings show that measurements of serum amyloid A concentration provide a valuable non-invasive aid in identifying acute renal allograft rejection, including that in patients whose graft does not function initially.     

Clinical application of real time-polymerase chain reaction in determining cytomegalovirus viral DNA load in renal transplant recipients

Background Cytomegalovirus (CMV) remains a significant clinical problem among immunosuppressed renal transplant patients.Quantitative PCR assays have become the most common methods in the determination of CMV infections in transplant patients.This study was to determine the relationship between CMV infection and the acute rejection of the transplanted kidney.Methods Plasma samples from 77 renal transplant patients that were pre-transplant negative for CMV infection were tested using real-time quantitative PCR and CMV gene-specific primers.The detected viral loads were retrospectively compared with the acute rejection rate and the chronic or mild rejection rates of the renal transplant.Results CMV-DNA was detected in 29 of 77 recipients,yielding a positive rate of detection of 37.7％ for this procedure.Twelve of the 21 recipients (57.1％) who suffered acute rejection had positive CMV-DNA.Among the 56 recipients suffered from chronic or mild rejection,17 (30.4％) had positive CMV-DNA plasma.Moreover,of the 29 recipients who had detectable CMV-DNA after transplant,12 (41.4％) suffered from acute rejection; of the 48 recipients with undetectable CMV-DNA,only nine (18.8％) developed acute rejection.Post-transplant patients with acute rejection had a higher rate (57.1％ vs.30.4％,P=0.03) of post-transplant CMV infection than those with chronic or mild rejection.Conclusion CMV infection is a risk factor of acute renal transplant rejection and CMV infection should be prevented and treated in renal transplant recipients.Chin Med J 2012; 125(19):3575-3577     

移植肾功能延迟恢复的临床研究

目的 探讨肾移植术后移植肾功能延迟恢复(DGF)的病因及诊治方法.方法 回顾性分析15例肾移植术后DGF患者的临床资料及诊治过程.15例DGF的病因不同,在血液透析的基础上,分别给予急性排斥反应冲击治疗、调整免疫抑制剂,近期移植肾切除后再次原位移植等方法进行治疗.结果 15例患者术后发生急性排斥8例;急性肾小管坏死5例;移植肾静脉血栓1例;环孢素A肾毒性1例,所有患者经治疗.肾功能在术后10～35 d恢复正常.随访0.5～3年,无并发症发生.结论 DGF是肾移植术后常见并发症之一,主要原因是急性排斥和急性肾小管坏死,区别不同原因采用相应治疗,可获得满意疗效.     

Effects of combined immune therapy on survival and Th1/Th2 cytokine balance in rat orthotopic liver transplantation

Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation. Methods The model of rat orthotopic liver transplantation was established by modified Kamada’s technique. Recipients were divided into group A (control group): SD→SD; group B (group of rejection): SD→Wistar without any treatment; group C: SD→Wistar with CsA monotherapy from day 1 to day 5; and group D: SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7. Results The survival period of recipients in groups A (&gt;60 days) and D (&gt;60 days) was significantly longer than that in group B (13.8±2.4 days). The serum levels of interleukin 2 (IL-2) and interferon γ in group B were significantly higher than those in other groups; the level of tumor necrosis factor α was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P&lt;0.05). Conclusions Combined immune therapy can prolong the survival of allografts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.