Application of various doses of mizoribine in clinical kidney transplantation

<正>Objective To observe efficacy and safety of different doses of mizoribine to prevent rejection after renal transplantation. Methods Sorted by time of operation and odevity,206 primary kidney transplant recipients were divided into 3 groups,including MMF group,MZR I group and MZR Ⅱ group. All recipients in 3 groups     

微嵌合体在母亲子女之间活体肾移植中的作用

目的 观察不同供受体关系亲属活体肾移植的临床疗效及其与微嵌合体之间的关系.方法 回顾性分析复旦大学附属中山医院2004-2008年130例亲属肾移植临床资料.受者随访1～5年,利用微卫星及性染色体决定基因聚合酶链反应(PCR)技术检测外周血DNA微嵌合体,并根据随访结果,分析微嵌合体的作用.结果 受者1-年人/肾存活率分别为93.8%和92.3%,各供受者组关系比较发现1-年人/肾存活率差异均无统计学意义(均P＞0.05).130例受者中46例(35.4%)行移植肾穿刺活检,病理结果证实发生急性排斥反应26例,急性排斥反应发生率为20.0%(26/130).26例中14例(53.8%)为母亲子女之间肾移植,12例(46.2%)为其他供受者关系肾移植.母亲子女肾移植中急排斥反应发生率为30.4%(14/46),高于其他供受者关系肾移植急性排斥反应发生率(14.3%,12/84,P=0.028).130例受者中43例术后不同时间进行了外周血微嵌合体检测,在其中16例母亲供肾的受者中,4例检测到微嵌合体,阳性率25.0%;27例其他供者的受者中,4例检测到微嵌合体,阳性率为14.8%;母亲供肾微嵌合体阳性率比其他关系高约1倍.微嵌合体阳性组急性排斥反应发生率较微嵌合体阴性组高约1倍.结论 母亲子女之间肾移植急性排斥发生率较高;母亲供肾的微嵌合率较高;微嵌合率高的组别急性排斥反应较高;母亲子女之间特殊的免疫学关系可能影响肾移植效果.

Abstract：

Objective To compare the microchimeric and rejection rates in living donor kidney transplant recipients in mother and child relations and other relations. Methods This retrospective singlecenter study enrolled 130 recipients to receive allografts from living related donors from 2004 to 2008 at our hospital. They were followed up for 1 - 5 years. The demographic data of the study population were analyzed by basic statistical methods. A total of 43 recipient blood samples were collected for the detection of microchimerism by the assays of short tandem repeat (STR) and sex-determining region-y gene (SRY)polymerase chain reaction (PCR). Results The 1-year patient/graft survival rates were 93.8% and 92.3% respectively. And there was no significant differences between mother and child group and other relative group. Forty-six biopsy samples were collected from 46 recipients. Twenty-six (20.0% ) cases had the occurrences of acute rejection episodes in different Banff degrees as proven by biopsy. 53. 8% ( 14/26)cases were mother and child renal transplantation, higher than other relative (46. 2%, 12/26) . The mother donor kidney transplant recipients had about a twice higher rejection rate ( 30.4% vs 14. 3%, P = 0.028 ) and a twice higher microchimeric rate(25. 0% vs 14. 8% )than other relative. Conclusion Compared with other relations, the mother donor kidney recipients tend to have higher rates of microchimerism and acute rejection. And the special immune effect in mothers and children renal transplantation may influence its outcomes.     

Marginal living donor in kidney transplantation: experience in a Chinese single center

Background Living donor kidney transplantation is becoming popular in China, whereas, in clinical situations, some kidney donors may be sub-optimal, namely marginal living donor. The present study aimed to evaluate the safety and efficacy of marginal living donor kidney transplantation in a Chinese single center.

Methods Between January 2001 and December 2009, 888 kidney transplantations were performed in our center; 149 were living donor kidney transplantations. The living donors and recipients were followed up regularly after the operation. Of the living donors, 30 donors were marginal, who were older than 60 years or suffered from kidney anomaly or some benign diseases. Among the non-marginal living kidney transplantations, 58 donors and recipients had complete peri-operative and follow-up data. We compared the marginal and non-marginal living donor kidney transplantations with regard to donor age, follow-up period, donor’s serum creatinine at the last follow-up, recipient’s serum creatinine at the last follow-up, and graft survival at the last follow-up.

Results The mean age of donors in the marginal and non-marginal living donors were (55±9) (37–66) and (43±12) (30–59) years. The mean follow-up times of the marginal and non-marginal groups were (26.4±13.4) months and (28.8±14.8) months. The donor and recipient serum creatinine levels at the last follow-up were (1.16±0.20) mg/dl and (1.30±0.24) mg/dl in the marginal group, and (1.12±0.32) mg/dl and (1.34±0.32) mg/dl in the non-marginal group. Three recipients in the marginal group and five recipients in the non-marginal group had acute rejection episodes during the first year. Actuarial 3-year graft survival was 96.7% in the marginal group and 100% in the non-marginal group. No significant differences were detected between the two groups with regard to these data.

Conclusion Utilization of highly selective marginal living donors can be a safe, feasible, and effective way for the treatment of patients with end stage renal disease.

     

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&lt;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.     

The mid-long term effect of conversion from cyclusporine to trcrolimus in patients with kidney

<正>Objective To verify the efficacy and safety of conversion from cyclosporine ( CsA) to tacrolimus ( Tac) in renal transplant recipients. Methods The clinical data of conversion from CsA to Tac in renal transplant recipients were retrospectively analyzed. In 97 petients undergoing kidney transplantation,there were 62 cases of chronic al-     

Daclizumab prevents acute renal allograft rejection. 1 year analysis

Objective To investigate the clinical effect of Daclizumab on preventing acute rejection in renal transplant recipients.Methods71 patients were randomly divided into two groupsDaclizumab group (n =26) and control group (n = 45). Baseline regimen of mycophenolate mofetil (MMF), cyclosporin (CsA), methylprednisolone (MPD) and prednisone (Pred) were administered to all patients. The treatment of Daclizumab was based on baseline regimen. The Daclizumab group received Daclizumab twice before and after renal transplant. The occurrence of post-transplantation acute rejection, renal function and T lymphocyte subtypes were sequentially monitored; meanwhile adverse events, infection episode, and patient and graft survival were observed.All of patients received a follow-up of 12 months at least. Results The occurrence of acute rejection in Daclizumab group in 1,3, 6 and 12 months after renal transplantation was 7.7%, 19.2%, 23.1% and 30.8%, respectively,while it was 15.6% ,28.9%,35.6% and 46.7% in the control group. There was significant difference between the two group(P ＜ 0.05). There was no difference in infection episodes and adverse events between the Daclizumab group and control group. One year patient survival was 92.3% in Daclizumab group, 91.1% in control group (P ＞ 0.05), compared with graft survival of 96.2 % and 93.3 % for Daclizumab and control group, respectively (P ＞ 0. 05). The renal function in Daclizumab group in 1, 6 and 12 months after renal transplantation was better than that in control group (P ＜ 0.05). The CD3 and CD4 subtypes decreased in both two groups after operation but no significant difference (P ＞ 0.05). ConclusionDaclizumab combined with MMF, CsA, MPD and Pred therapeutic regimen was effective to reduce the occurrence of acute rejection in renal transplant recipients and have no influence on T lymphocyte subtypes.     

PREVENTION AND TREATMENT OF REJECTION AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

Objective To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) tran splantation. Methods Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg· d-1) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg· kg-1 on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. Results No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 ± 11 μmol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g·d-1) for 3 days. OKT3 (0.5 mg·d-1) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. Conclusion Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.     

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.

     

Clinical observation of the effect of tacrolimus（Prograf）against renal allograft rejection in 294 cases

Abstaract Objective:To study the effect of tacrolimus (Prograf ,FK506) in preventingrenal allograft reject-tion.Methods:The curative effect, therapy index,toxicity and side effects of FK506 were observed in 294 renal transplant recipients among whom 268 received FK506 24h after the operation and the other 26 with cyclosporine(CsA) developed actue rejection after transplantation and wee given FK506 to replace methyl-prednisolone(MP) when the latter did not result.All the patients were given oral mycophenolate mofetil (MMF,1.0g/d)and meticorten(Pred,30mg/d)24h later after operation.Results:In the 268 recipients previously mentioned,the incidence of acute rejection wsas 10.45%,blycometabolism disorder 9.33% ,ner-vous system disturbance 1.59%,liver function abnormality 2.99%,nephrotoxicity 1.87%,gastrointestinal disorder 17.5%,cytomegalovirus(CMV) viremia 2.99%,and non-CMV pulmonary infection 1.59%(4/268) ,with 1 fatal case for cerebral hemorrhage with normal allograft function and another 2 non-fatal cases in which function loss resulted in removal of the allografts.The blood trough concentrations of FK506 were between 5 and 20μg/L.In thd 26 cases of steroid-resistant rejection,23(88.46%,23/26)were re-versed and the rest 3 required plasma exchange and application of OKT3 before recovery.Conclusion:As a safe and effective immunosuppressant,FK506 can reduce the incidence of allograft rejection in kidney trans-plant recipients with little side effects or toxicity, which is particularly applicable in patients with steroid-re-sistant rejection or CsA nephrotoxicity.Attention should to be paid to glycometabolism disorder due to FK506,however ,the long-term effects of FK506 need further investigation.     

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.     

肾移植术后受者体质量指数对其死亡的影响分析

【目的】探究肾移植术后受者体质量指数对其死亡的影响。【方法】回顾分析本院2001～2010年死亡的207例肾移植受者资料。根据受者术后随访期间的身体质量指数（BM I ）将其分为偏瘦组（BM I＜18．5 kg/m2,n ＝55）、正常组（18．5 kg/m2≤BMI＜24k g/m2,n＝100）和超重组（BMI≥24 kg/m2,n＝52）,对三组受者死亡原因、受者存活率和移植肾存活率进行比较分析。【结果】所有受者的前三位死亡原因依次为感染（31．9％）、心血管疾病（21．3％）和肝功能衰竭（15．9％）;超重组中移植肾失功能死亡和因心血管疾病死亡的比率均明显高于偏瘦组和正常组（P＜0．05）;正常组肾移植术后受者存活率明显高于偏瘦组和超重组（P ＜0．05）;正常组术后3年、5年受者存活率明显高于偏瘦组和超重组（P＜0．05）,但1年、10年受者存活率三组比较无统计学差异（P＞0．05）;正常组肾移植术后移植肾存活率明显高于偏瘦组和超重组（ P＜0．05）。【结论】肾移植术后受者BM I≥24 kg/m2是增加心血管疾病死亡和降低受者及移植肾存活率的一个风险因素。     

Cytomegalovirus infection as a complication of OKT3 therapy in kidney transplant recipients

We compared the incidence of clinical CMV illness in 25 renal transplant recipients treated with OKT3 for steroid resistant cellular rejection with 88 renal transplant patients treated only with conventional immunosuppression (cyclosporin A and steroids). Nine (36%) patients in the OKT3 group developed CMV illness compared to (2.3%) amongst those treated conventionally (p<0.0005). Patients who received OKT3 were divided into four groups according to the CMV antibody status of the donor and recipient. Six of the 9 episodes of CMV infection occurred in patients not previously exposed to CMV, who received a kidney from a CMV positive donor. Three (12%) of the patients treated with OKT3 died of CMV disease. A further 2 patients died of other causes giving an overall mortality in the OKT3 treated group of 20%. We concluded that when OKT3 therapy is used in association with donor/recipient CMV mismatch it is associated with a high CMV morbidity and mortality.     

肾移植受者免疫抑制维持治疗期霉酚酸酯剂量与霉酚酸暴露的关系

目的 观察服用霉酚酸酯(MMF)的肾移植受者在免疫抑制维持治疗期霉酚酸(MPA)的暴露水平.方法 60例肾移植受者均采用环孢素A(CsA)、MMF和强的松(Pred)三联免疫抑制方案,于服用MMF后0.5、2、4h采集外周静脉血,通过酶增强免疫分析技术测定血浆MPA浓度,以有限采样法的简化公式计算肾移植受者MPA血药浓度—时间曲线下面积(AUC).根据口服MMF剂量,将患者分为3组:MMF低剂量组(MMF＜1.5 g/d,n=18)、MMF推荐剂量组(MMF=1.5 g/d,n =29)、MMF高剂量组(MMF＞1.5 g/d,n=13).根据MPA AUC值,将患者分为MPA低暴露组(MPA AUC＜30 mg·h·L-1).MPA目标暴露组(MPAAUC =30～60 mg·h·L-1)、MPA高暴露组(MPA AUC＞60 mg.h·L-1).结果 60例肾移植受者MPA AUC平均值为(59.83±19.42)mg·h·L-1;其中,MPA低暴露组3例(5.0％),MPA目标暴露组31例(51.7％),MPA高暴露组26例(43.3％);三组CsA平均用量分别为(166.67±14.43) mg/d、( 137.10 ±41.27) mg/d和(128.85±37.88) mg/d,呈递减趋势,但组间差异无统计学意义(P＞0.05).结论 在未监测MPA AUC水平而仅根据临床事件调整MMF用量的情况下,肾移植受者平均MPA暴露水平偏高;MPA药代动力学在不同个体间存在较大的差异,进行MMF的治疗药物监测可能是必要的.     

Simulect和OKT3诱导治疗应用于肾移植临床的疗效比较

目的评价Simulect和OKT3作为肾移植诱导治疗的有效性和安全性.方法将170例首次肾移植受者随机分为两组:Simulect组62,OKT3组108例.所有患者免疫抑制维持治疗均用环孢素A(CsA)/他克莫司(FK506) 霉酚酸酯(MMF) 泼尼松(Pred)三联.Simulect组:分别于术前2 h和术后4 d使用20mg Simulect:OKT3组:OKT3每天5 mg静滴,从术后第1天开始,连用7～10 d.观察两组在肾移植术后1年内急性排斥反应(AR)、移植肾功能延迟恢复(DGF)、毒副作用和人/肾存活情况.结果有34例发生AR,Sinulect组6例,OKT3组28例(P＜0.05),其中OKT3组5例出现2次或2次以上AR,7例AR需要ATG治疗逆转.移植肾功能延迟恢复(DGF)、细胞因子释放综合征、过敏反应等方面,Simulect组发生率明显低于OKT3组(6vs32,0vs49,0vs31,P＜0.01).Simulect组感染发生率低于OKT3组(16vs45;P＜0.05).OKT3组有2例移植肾切除,1例死于严重肺部感染.结论Simulect在肾移植免疫诱导治疗中疗效显著,副作用少,是一种强效安全的免疫抑制剂.     

肾移植受者BK病毒感染的临床诊断及治疗

目的 探讨肾移植受者BK病毒(BKV)感染的诊断及治疗方法.方法 选取肾移植术后48个月内的患者共227例.采集其血、尿样本,行BKV尿沉渣细胞学计数与实时荧光定量PCR检测病毒拷贝.对部分肾移植受者进行移植肾活检.将尿或血中BKV DNA阳性患者80例分成干预组(51例)与对照组(29例).干预组进行调整免疫抑制剂:19例环孢素A(CsA)减量,22例他克莫司(FK506)减量,10例FK506转换成CsA;对照组不进行干预,并且密切监测急性排斥反应.干预3个月后再次检测,比较组内和组间干预前后BKV活化指标的差异.结果 227例受者的尿decoy细胞、BK病毒尿症与病毒血症的阳性率分别为33.O%、33.5%和15.4%.干预组干预后尿decoy细胞、尿和血BKV数量的中位水平均为O,明显低于干预前(5.0个/10HP,1.50 x 104拷贝/ml,0拷贝/ml,均P<0.01).对照组观察前后尿decoy细胞、血BKV数量的中位水平差异无统计学意义(6.0个/10HPvs 5.0个/10HP、0拷贝/ml vs 0拷贝/ml,均P>0.05),尿BKV数量观察结束时上升(观察前:0.79×104拷贝/ml,观察后:2.21 x104拷贝/ml,P<0.01).上述各项指标干预前后的差值在干预组与对照组间差异均有统计学意义(均P<0.05).干预过程中所有患者均未出现急性排斥反应.确诊BKV相关性肾病4例,其干预治疗后尿decoy细胞计数以及血、尿BKV DNA均明显降低,移植肾功能有所恢复.结论 定量尿沉渣细胞学检测简单、易行、敏感,可以作为BKV活化的指标,间接反映肾脏病理情况.也可检测血、尿BKV DNA了解病毒活化情况、筛查BKV相关的移植肾肾病.减少免疫抑制剂剂量或换FKS06为CsA治疗肾移植术后BKV感染效果良好.     

联合检测血清HLA-G5和sCD30水平对评价肾移植受者免疫状态的价值

目的 研究肾移植受者血清人类白细胞抗原G5(HLA-G5)、可溶性CD30(sCD30)的表达与移植肾功能的关系,以及联合两者评价肾移植受者免疫状态的最佳诊断阈值、敏感度及特异度.方法 选取2002年1月至2008年11月西安交通大学医学院第一附属医院肾病中心接受同种异体肾移植手术受者66例,其中38例移植肾功能正常,15例为急性排斥反应,13例为慢性排斥反应.检测所有受者血清HLA-G5、sCD30的表达水平;应用受试者工作特征曲线分析HLA-G5联合sCD30评价移植术后1年内及术后1年以上不同免疫状态的最佳临界值、敏感度和特异度.结果 HLA-G5水平与血肌酐水平相关(r=-0.493,P＜0.01),sCD30水平与血肌酐水平相关(r=0.691,P＜0.01).术后1年内,当HLA-G5临界值取82μg/L,sCD30 临界值取12.2μg/L时,评价肾移植受者免疫状态的敏感度为7 8.6%,特异度为85.7%;术后1年以上,当HLA-G5临界值取141μg/L,sCD30临界值取10.3 μg/L时,评价肾移植受者免疫状态的敏感度为92.3%,特异度为84.6%.结论 血清HLA-G5联合sCD30可作为反映肾移植受者免疫状态简便而有效的临床指标.     

重组抗表皮生长因子受体人鼠嵌合单克隆抗体治疗晚期恶性肿瘤Ⅰ期临床试验

目的 评价重组抗表皮生长因子受体(EGFR)人鼠嵌合单克隆抗体(CMAB009)在晚期肿瘤患者中的药代动力学特点和安全性,初步观察疗效.方法 单中心、开放的Ⅰ期临床试验.试验分单次和多次给药两阶段.单次给药设100、250、400mg/m2三个剂量组,随后的多次给药分两组,A组为250 mg/m2,每周一次,连用4周;B组起始剂量400mg/m2,以后每周250 mg/m2,连用4周.多次给药后部分缓解(PR)或稳定(SD)的患者,继续每周给药250 mg/m2,直至病情进展或无法耐受.结果 2008年1～8月,共入组18例受试者,均来自中国医学科学院肿瘤医院.其中结直肠癌10例,非小细胞肺癌7例,胃癌1例.未观察到3/4级不良反应.1/2级不良反应主要有皮疹、甲沟炎、发热、恶心和头痛.2例(13.3%)结直肠癌患者获得PR,至疾病进展时间(TTP)分别为24和16周.结论 CMAB009的耐受性良好,不良反应均为1～2级,最常见的不良反应为皮疹和甲沟炎,可以观察到抗肿瘤疗效.

Abstract：

Objective To characterize the safety profiles and serum pharmacokinetic effects of antiepidermal growth factor receptor monoclonal antibody (CMAB009) in advanced cancer patients and evaluate the preliminary evidence of its anti-tumor activity. Methods This phase I, single-center clinical trial had 2 phases of treatment: single-dose phase, followed by a fixed weekly dose. Subjects meeting the inclusion criteria were enrolled. The subjects were randomly assigned to receive 1 of 3 initial doses of CMAB009 (100, 250 & 400 mg/m2) for the purpose of single-dose pharmacokinetic evaluation. After a 28-day washout period of allowing for the characterization of pharmacokinetic end points, the eligible patients were permitted to undergo a successive multi-dose phase study. They were divided into 2 dose groups, group A with 4 weekly doses of 250 mg/m2, group B with the initial dose of 400 mg/m2, followed by 3 weekly doses of 250 mg/m2. The subjects were closely monitored for adverse events throughout the trial. Results A total of 18 subjects were recruited, including colorectal cancer ( n = 10), non-small cell lung cancer ( n =7) and gastric cancer (n = 1 ). CMAB009-associated toxicity was minimal. And the most commonly reported Grade 1/2 adverse events were skin rashes, fever, nausea and headache. Two patients with colorectal cancer achieved partial remission and the time to progression (TTP) was 24 and 16 weeks respectively. Conclusion As a well-tolerated antitumor agent, CMAB009 may be safely administered by the above multi-dosing protocol.     

不同剂量雷公藤多苷治疗肾移植后蛋白尿临床研究

目的 观察不同剂量雷公藤多苷治疗肾移植术后蛋白尿的临床效果.方法 选择肾移植术后出现蛋白尿患者45例,按随机数字法分为3组,足量雷公藤多苷组(常规组)、半量雷公藤多苷组(半量组)、对照组各15例.常规组在应用免疫抑制剂基础上用雷公藤多苷1 mg/(kg·d)治疗.半量组在应用免疫制剂基础上用雷公藤多苷0.5 mg/(kg·d)治疗,对照组应用免疫抑制剂.观察三组患者治疗后24h尿蛋白定量、尿素氮、肌酐、环孢素用量及副作用.结果 常规组、半量组均能明显减少蛋白尿,24h蛋白定量均低于对照组(P<0.05).常规组、半量组患者环孢素用量低于对照组(P<0.05).半量组副作用低于常规组.结论 雷公藤多苷能明显减少肾移植术后出现蛋白尿患者的蛋白尿.达到保护移植肾肾功能及减少环孢素用量.长期应用半量雷公藤多苷能达到常规雷公藤多苷相同治疗效果,副作用轻.