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。     

致敏受者肾移植急性排斥反应的影响因素

目的 探讨致敏受者肾移植急性排斥反应的影响因素。方法 对102例术前致敏患者临床资料进行回顾性分析,探讨群体反应抗体(PRA)水平、氨基酸残基配型、术后PRA水平升高及细胞因子基因型对急性排斥反应发生率的影响。结果和结论 102例致敏肾移植受者术后随访期间发生急性排斥反应33例次,其中PRA水平、氨基酸残基相配程度、术后PRA水平升高、TNF-α高产量基因型和IL-10高产量基因型对移植肾的急性排斥发生率均有显著性影响。术前综合评估这些因素,有利于制订合理的免疫抑制方案。     

致敏受者肾移植急性排斥反应的影响因素

目的：探讨致敏受者肾移植急性排斥反应的影响因素。方法：对102例术前致敏患者临床资料进行回顾性分析．探讨群体反应抗体(PRA)水平、氨基酸残基配型、术后PRA水平升高及细胞因子基因型对急性排斥反应发生率的影响。结果和结论：102例致敏肾移植受者术后随访期间发生急性排斥反应33例次，其中PRA水平、氨基酸残基相配程度、术后PRA水平升高、TNF-α高产量基因型和IL-10高产量基因型对移植肾的急性排斥发生率均有显著性影响。术前综合评估这些因素，有利于制订合理的免疫抑制方案。     

肾移植术后近期脑梗死危险因素分析

目的探讨肾移植术后患者近期发生脑梗死的危险因素。方法13例肾移植术后近期发生脑梗死的患者,回顾性分析其移植前及移植后第1、2、3个月的平均血压、空腹血糖、总胆固醇、甘油三酯、血肌酐水平以及环孢素(CsA)或他可莫司(FK506)浓度。结果肾移植术后患者血脂和血糖均明显升高(P<0.05),肾移植术后脑梗死患者血肌酐水平较术前明显降低(P<0.05),平均血压水平与手术后3个月比较差异无统计学意义(P>0.05)。结论影响近期肾移植术后病人发生脑梗死的主要危险因素是肾功能,空腹血糖以及血脂水平;且血糖、总胆固醇、甘油三酯水平和CsA或FK506浓度有相关性。     

肝、肾移植患者并发血流感染的死亡危险因素分析

目的:评价影响伴有血流感染的肝、肾移植患者生存率的可能危险因素。方法:回顾性研究103例肝、肾移植患者发生的138次血流感染,评估导致肝、肾移植术后患者死亡的危险因素。使用单变量分析和多元逻辑回归方法确定危险因素。结果:入选患者年龄12~66(42.3±12.7)岁。绝大多数为院内感染(78.6%),血流感染相关的死亡率为39.8%(41/103)。单变量分析显示以下变量能预测血流感染相关的死亡:腹腔内或胆道感染(P=0.003),混合感染(P<0.001),肝移植(P<0.001),血小板计数<50000/mm3(P<0.001),感染性休克(P<0.001)。多元逻辑回归分析显示血小板计数<50000/mm3(P=0.002)和感染性休克(P<0.001)是独立的死亡危险因素。结论:伴有血流感染的肝、肾移植患者死亡率升高的独立危险因素包括血小板计数下降和感染性休克。血流感染一旦发生死亡率极高,预防肝、肾移植术后患者血流感染的发生十分重要。     

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.

     

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.

     

Establishment of a sensitized canine model for kidney transplantation

Objective:To establish a sensitized canine model for kidney transplantation. Methods: 12 male dogs were averagely grouped as donors and recipients. A small number of donor canine lymphocytes was infused into different anatomic locations of a paired canine recipient for each time and which was repeated weekly. Specific immune sensitization was monitored by means of Complement Dependent Cytotoxicity (CDC) and Mixed Lymphocyte Culture (MLC) test. When CDC test conversed to be positive and MLC test showed a significant proliferation of reactive lymphocytes of canine recipients, the right kidneys of the paired dogs were excised and transplanted to each other concurrently. Injury of renal allograft function was scheduled determined by ECT dynamic kidney photography and pathologic investigation. Results:CDC test usually conversed to be positive and reactive lymphocytes of canine recipients were also observed to be proliferated significantly in MLC test after 3 to 4 times of canine donor lymphocyte infusions. Renal allograft function deterioration occurred 4 d post-operatively in 4 of 6 canine recipients, in contrast to none in control dogs. Pathologic changes suggested antibody-mediated rejection (delayed) or acute rejection in 3 excised renal allograft of sensitized dogs. Seven days after operation, all sensitized dogs had lost graft function, pathologic changes of which showed that the renal allografts were seriously rejected. 2 of 3 dogs in control group were also acutely rejected. Conclusion：A convenient method by means of repeated stimulation of canine lymphocyte may induce specific immune sensitization in canine recipients. Renal allografts in sensitized dogs will be earlier rejected and result in a more deteriorated graft function.     

心脏死亡供体的移植肾功能延迟恢复的危险因素分析

目的:探讨心脏死亡供体(death cardiac donor, DCD) 的移植肾肾功能延迟恢复(delayed gra function, DGF) 发生的危险因素及预后情况。方法:收集中南大学湘雅三医院器官移植中心及武汉中南医院2010 年2 月至2012年3 月的48 例DCD 肾移植受者, 分为DGF 组(n=18) 及肾功能稳定(immediate gra function, IGF) 组(n=30)。分析发生DGF 的危险因素。结果:DGF 的发生率为37.5%, 在单因素分析中受者术前透析时间(P<0.001)、HLA 错配位点(P<0.001)、脑出血死亡供体(P=0.011)、供者BMI (P<0.001)、术前SCr (P<0.001)、使用去甲肾上腺素(P<0.001)、热缺血时间 (P<0.001)、冷缺血时间 (P<0.001) 为DGF 的危险因素, 在多因素分析中, 受体术前透析时间≥12 个月(P=0.060, OR=15.060)、脑出血死亡供体(P=0.022, OR=39.652)、供体术前SCr≥177 μmol/L (P=0.008, OR=57.148) 为DGF 独立的危险因素。结论:DGF 的独立危险因子是受体术前透析时间≥12 个月、供体术前SCr≥177 μmol/L、脑出血死亡供体。     

Risk factors and incidence of posttransplant diabetes mellitus in Mexican kidney recipients

BACKGROUND: Many risk factors are associated with the development of posttransplant diabetes mellitus (PTDM), which has adverse effects on graft and patient survival. We report the incidence and risk factors associated with the development of PTDM in Mexican kidney recipients. METHODS: In a retrospective cohort study, we included kidney transplants performed between January 1, 1994 and December 31, 2000; all patients were followed up for at least 1 year posttransplantation. PTDM was defined as fasting blood glucose >126 mg/dL on at least two occasions. Statistical analysis included estimation of crude relative risk (RR) with 95% confidence intervals (CI). Adjusted RR and 95% CI by logistic regression were used. RESULTS: We studied 522 kidney recipients. Fifty three (10.1%) cases of PTDM were identified in this cohort. Cumulative dosage of prednisone (PDN) >13 g (RR 7.6, 95% CI 1.5-16.3 p <0.0001) and the presence of >or=1 acute rejection episodes (RR 3.7, 95% CI 1.2-11.6 p <0.001 were independent risk factors associated with the development of PTDM. Obesity (RR 2.6, 95% CI 0.8-8.7, p = 0.083) and age range of 40-49 years (RR 2.0; 95% CI 0.6-7.2, p = 0.093) were identified as marginal risk factors. CONCLUSIONS: The incidence of PTDM in kidney recipients was 10.1% in our population. Cumulative PDN dosage and presence of >or=1 acute rejection episodes were independent risk factors for the development of PTDM. These results are consistent with prior studies of the diabetogenic effect of the PDN. The relationship between acute rejection and PTDM deserves further investigation in order to learn more about the role that inflammatory mechanisms may play in this association.     

肾移植术后急性体液性排斥反应的治疗

目的探讨肾移植术后急性体液性排斥反应的治疗方案。方法对12例肾移植术后的急性体液性排斥反应采用抗胸腺球蛋白（ATG，100mg／d&#215;5d）、血浆置换（PP，1～3次）和大剂量丙种球蛋白（IVIG，每周1．0g／kg，分2～3次静脉滴注）联合治疗。结果12例患者排斥反应均逆转。1例患者并发急性肾小管坏死。抗排斥治疗期间未发生严重感染性并发症。随访12～38个月，1例患者在术后16个月因慢性排斥反应恢复血液透析，其余患者移植肾功能良好。结论ATG联合PP—WIG能有效逆转肾移植术后急性体液性排斥反应，成功率高，并发症少。     

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.

     

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.     

Effect of desensitization treatment for highly sensitized uremic patients before kidney transplantation

<正>Objective To investigate the clinical features of bilateral native pelvic and ureteral transitional cell carcinoma ( TCC) in renal transplant patients. Methods A retrospective analysis was carried out on 16 patients with     

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.     

135例肾移植受者移植物丢失的原因分析

目的 探讨肾移植术后受者移植肾丢失的原因。方法 回顾性分析 2002年1月1日~2022 年1月1日在中国人民解放军总医院第八医学中心肾移植术后移植物发生丢失的135例受者临床资料。结果 受者移植肾丢失135例,移植肾丢失原因包括排斥反应70例（51.8%）、受者带功能死亡37例（27.4%）、外科并发症12例（8.9%）、药物毒性4例（3.0%）、耐碳青霉烯肺炎克雷伯菌感染4例（3.0%）、多瘤病毒相关性肾病3例（2.2%）、原发性无功能肾2例（1.5%）、原发病复发2例（1.5%）、肾前性急性肾衰1例（0.7%）。结论 肾移植术后受者移植物丢失原因主要原因是排斥反应,次要原因是受者带功能死亡,其他原因少见。     

同种异体肾移植30例的护理

目的：总结同种异体肾移植的治疗效果及护理体会。方法：对30例慢性肾功能衰竭患者施行同种异体肾移植术,术后采用三联免疫治疗方案。结果：1年存活率为96.7%,3年存活率为90%,平均住院25.5d。结论：完善的肾移植术后护理措施对患者的治疗、预后有积极影响,对提高生存率、提高远期生活质量有重要意义。