肾移植患者术后早期应用霉酚酸酯的临床观察

目的 观察肾移植术后早期不同剂量霉酚酸酯（ＭＭＦ）与环孢素Ａ（ＣｓＡ）和泼尼松（Ｐｒｅｄ）联用预防急性排斥反应的效果及安全性。方法 将６４例肾移植患者分为３组,分别给予ＭＭＦ２．０ｇ／ｄ（Ａ组）、１．５ｇ／ｄ（Ｂ组）及Ａｚａ ５０～１００ｍｇ／ｄ（Ｃ组）,每组均联用ＣｓＡ及Ｐｒｅｄ（剂量相同）。观察肾移植术后６个月内急性排斥反应的发生率、移植肾功能及药物的副作用。结果 Ａ、Ｂ、Ｃ组急性排斥反应的发     

骁悉与小剂量环孢素A在尸体肾移植中的联合应用

为观察骁悉（ＭＭＦ）与小剂量环孢素Ａ（ＣｓＡ）联合应用于尸体肾移植中的效果，将１６例患者随机分为３组，ＭＭＦ２．０ｇ组（ＭＭＦ用量为２．０ｇ／ｄ）；ＭＭＦ１．５ｇ组（ＭＭＦ用量为１．５ｇ／ｄ）；硫唑嘌呤（Ａｚａ）组。３组患者均同时接受相似剂量的ＣｓＡ和类固醇治疗。结果ＭＭＦ２．０ｇ组未发生急性排斥；ＭＭＦ１．５ｇ组１例（１／５）患者先后发生２次排斥；Ａｚａ组３例（３／５）患者各发生１次排斥。术后６个月ＭＭＦ２．０ｇ组患者血清肌酐值明显低于Ａｚａ组，其所用的ＣｓＡ剂量低于Ａｚａ组。认为ＭＭＦ无明显肝、肾毒性，每天２．０ｇ口服，并与小剂量ＣｓＡ和类固醇联合应用，临床疗效明显优于传统的三联疗法。     

骁悉和环孢素-A预防肾移植术后早期急性排斥反应

目的 探讨骁悉和环孢素－Ａ预防肾移植术后早期急性排斥反应的效果。方法 回顾性分析１９９７年１２月￣１９９９年１月临床资料完整肾移植患者１４６例,随访时间６￣１６个月。根据应用免疫抑制剂方案的不同分为硫唑嘌呤（Ａｚａ）组（环孢素－Ａ、泼尼松龙、Ａｚａ）和骁悉（ＭＭＦ）组（环孢素－Ａ、泼尼松、ＭＭＦ）。其中Ａｚａ组７８例,ＭＭＦ组６８例。所有受者术前行人类白细胞抗原（ＨＬＡ）配型,ＨＬＡ错配≤３个位点     

丙型肝炎病毒RNA阳性的肾移植受者免疫抑制剂的应用

目的 探讨肾移植术后发生丙型肝炎的受者合理的免疫抑制方案。方法 将２５例丙型肝炎病毒ＲＮＡ（ＨＣＶ ＲＮＡ）阳性的患者分为３组,分别给予硫唑嘌呤（Ａｚａ）＋环孢素Ａ（ＣｓＡ）＋泼尼松（Ｒｒｅｄ）（Ａｚａ组）、霉酚酸酯（ＭＭＦ）＋ＣｓＡ＋Ｐｒｅｄ（ＭＭＦ组）和ＭＭＦ＋Ｐｒｅｄ,并以３０例ＨＣＶ ＲＮＡ阴性受者为对照。结果Ａｚａ组和８／１２的患者肝功能发生异常;ＭＭＦ组有２／８的患者肝功能发生异常;Ｍ     

用于肾移植的几种免疫抑制方案的对比研究

目的 比较肾移植后几种常用免疫抑制治疗方案的疗效与副作用。方法 根据所使用的免疫抑制治疗方案将８７例肾移植患者分为４组,Ａ组的免疫抑制治疗方案为他克莫司（ＦＫ５０６）、霉酚酸酯（ＭＭＦ）和泼尼松（Ｐｒｅｄ）;Ｂ线为环孢素Ａ（ＣｓＡ）、ＭＭＦ和Ｐｒｅｄ;Ｃ组为ＣｓＡ、硫唑嘌呤（Ａｚａ）和Ｐｒｅｄ;Ｄ组为ＣｓＡ和Ｐｒｅｄ。观察术后移植肾功能的恢复情况、排斥反应发生率、并发症及免疫抑制剂用量的变化。结果     

霉酚酸酯在肾移植后肝功能不良患者中的应用

目的 分析和评价肾移植后肝功能不良患者使用霉酚酸酯（ＭＭＦ）的有效性和安全性。方法 １２例患者术后免疫抑制方案为：９例采用环孢素Ａ（ＣｓＡ）、硫唑嘌呤（Ａｚａ）、泼尼松（Ｐｒｅｄ）;３例采用ＣｓＡ、Ｐｒｅｄ。发生肝功能不良后,停用Ａｚａ;９例采用三联治疗的患者,６例减少ＣｓＡ和量１／４－１／３,３例改用ＣｓＡ、Ｐｒｅｄ;３例采用二联治疗者,１例减少ＣｓＡ,２例停用ＣｓＡ;１２例均加用ＭＭＦ１．５～     

CsA顺序用药对肾移植长期存活的影响

目的：探讨ＣｓＡ顺序用药对肾移植长期存活的影响。方法：随机选择３２例肾移植患者术后立即应用ＯＫＴ３,并以同期５６例术后立即应用ＣｓＡ的患者为对照。结果：ＯＫＴ３组及ＣｓＡ组急性排斥反应（ＡＲ）发生率分别为３４．４％和６４．３％（Ｐ〈０．０１）,难治性排斥反应发生率ＯＫＴ３组为９．１％,ＣｓＡ组为３０．６％（Ｐ〈０．０５）。术后首次ＡＲ发生时间,ＣｓＡ组为１３．１±１．３ｄ,ＯＫＴ３组为２２．５±３     

肾移植术后应用FK506抗排斥治疗的临床研究

目的　观察ＦＫ５０６ 在肾移植术后抗排斥治疗的效果及副作用。　方法　对肾移植术后单独应用环孢素Ａ（ＣｓＡ）５０ 例和术后应用ＦＫ５０６ ５０ 例（ 术后２４ 小时应用ＦＫ５０６ ４０ 例,ＣｓＡ 中毒后改ＦＫ５０６ １０ 例）患者进行比较。　结果　ＣｓＡ 组发生急性排斥反应（ＡＲ）９ 例,发生率为１８ ％ ,逆转８ 例（８８ ％） ,肾功能在２ ～２６ 天恢复正常３８ 例（７６ ％） ,肺部感染２ 例,泌尿系感染１ 例,肾中毒２例,肝中毒３ 例,高血糖２ 例,腹泻１ 例,摘肾１ 例。ＦＫ５０６ 组ＡＲ４ 例均逆转,肾功能２～１３ 天恢复正常４０ 例（８０％ ）,高血糖１４ 例（２８％ ）,肾中毒２ 例,肝中毒１ 例,腹泻２２ 例（４４％ ）,１ 例因肺部感染、高血糖难以控制仍改用ＣｓＡ。应用ＣｓＡ 肝中毒的１０ 例患者改用ＦＫ５０６ 后肝功能７ ～１６ 天全部恢复正常。　结论　肾移植术后应用ＦＫ５０６ 安全有效,排斥率明显降低,副作用小,但对长期存活的影响及并发症还需进一步观察。     

尸体肾移植术后137例急性排斥反应的治疗体会

自１９８５年２月至１９９３年３月施行尸体肾移植４７５例，术后均应用环抱素Ａ（ＣｓＡ）、硫唑嘌呤（Ａｚａ）及强的松（Ｐｒｅｄ）治疗，其中发生急性排斥反应（ＡＲ）１３７例（２８．８％），经正确的使用免疫抑制剂，并分别应用甲基强的松龙（ＭＰ），ＯＫＴ３及ＡＬＧ冲击治疗，９６例逆转（７０．０％），２９例摘除移植肾（２１．２％），１２例死亡（８．８％）。就发生ＡＲ的原因，诊断与鉴别诊断及处理进行讨论。     

PRA、HLA配型技术在肾移植中的应用

目的 探讨群体反应性抗体（ＰＲＡ）、ＨＬＡ配型技术对肾移植近远期效果的影响。方法对等待肾移植的１０２０例患者采用ＰＲＡ测定、ＨＬＡ组织配型,ＰＲＡ阴性或阳性者均经血浆置换,ＨＬＡ抗原３～６个位点相合为第一组;未采用ＰＲＡ、ＨＬＡ组织配型的４２３例患者为第二组。观察两组肾移植术后免疫指标的变化,近期急性排斥反应发生率以及ＨＬＡ－Ａ、Ｂ、ＤＲ位点对长期存活的影响。结果 第一组肾移植术后环孢素Ａ（ＣｓＡ     

Comparison between mycophenolate mofetil- and azathioprine-based immunosuppressions in clinical lung transplantation.

BACKGROUND: The aim of the study was to assess the impact of mycophenolate mofetil (MMF) on the early phase after lung transplantation. PATIENTS AND METHODS: Thirty-eight consecutive patients between November 1994 and January 1997 were treated with cyclosporine, prednisolone, antithymocyte globuline induction therapy, and either MMF (n = 21) or azathioprine (Aza) (n = 17). Four patients from the MMF group and 2 patients from the Aza group were intubated and in the ICU prior to transplantation. Demographic data and primary diagnosis were comparable. MMF was administered at a dosage of 2 gm/day whereas Aza was initiated at 2 mg/kg/day and adapted by leukocyte count. Three-month survival and incidence of rejections and infections were compared. RESULTS: Six-month survival in the MMF group was 76% compared to 65% in the Aza group (n.s.). The mean number of acute rejection episodes in the MMF and Aza group were 0.29+/-0.10 and 1.53+/-0.29 (p<0.01) respectively. Transbronchial biopsy (TBB) results > or =grade 2 ISHLT were seen in 10% of MMF and in 43% of Aza-treated patients; completely free from rejection were 17 MMF and 3 Aza patients. The mean number of infections per patient in the MMF and Aza group were 1.57+/-0.29 and 2.29+/-0.40 respectively, bacterial (1.10 vs. 1.71), viral (0.35 vs. 0.33), and fungal (0.14 vs. 0.24) infections were the same in both groups. CONCLUSIONS: These data result suggest that mycophenolate mofetil therapy is more effective in preventing rejection episodes in patients early after lung transplantation than therapy with azathioprine. We therefore conclude that MMF is a safe and effective drug to optimize immunosuppressive therapy in the early phase after lung transplantation.     

Mycophenolate mofetil does not modify the incidence of cytomegalovirus (CMV) disease after kidney transplantation but prevents CMV-induced chronic graft dysfunction.

Ganciclovir, which is used to treat cytomegalovirus (CMV) infection, has been shown in rodent models to abolish CMV-mediated chronic cellular damage and endothelial cell proliferation; when associated with mycophenolate mofetil (MMF), it has been shown to increase its anti-herpes virus activity. This study tested the hypothesis that kidney graft recipients who received antirejection prophylaxis with MMF and who were treated with ganciclovir for a declared CMV disease could be protected from chronic graft dysfunction. Investigated was the impact of ganciclovir-treated CMV diseases in consecutive first kidney recipients according to their immunosuppressive therapy. The azathioprine (Aza)-treated group (Aza group) included 319 patients. The MMF-treated group (MMF group) included 126 patients. CMV disease was clinically defined and confirmed by virological proof of CMV infection and was treated for at least 14 d with ganciclovir. Despite having the same incidence (21.6% in the Aza group versus 24.6% in the MMF group) and severity, CMV disease was significantly associated with graft loss independent of acute rejection episodes or other factors when tested in a Cox proportional model in the Aza group only (P < 10(-4)). It was shown for the first time that patients whose CMV disease is treated with ganciclovir while they are on MMF therapy are protected from the long-term deleterious consequences of CMV disease on graft survival, independent of acute rejection. It is suggested that the enhanced anti-herpes virus activity of ganciclovir by MMF could contribute to this reported effect, which may represent a significant contribution of MMF efficacy to graft survival.     

雷公藤多苷对移植肾长期存活率的影响

目的:探讨雷公藤多苷(TW)作为免疫抑制剂对肾移植患者长期存活率的疗效及副作用.方法:104例患者在肾移植术后采用TW 泼尼松(Pred) 环孢霉素(GsA) 硫唑嘌呤(AZa)免疫抑制剂治疗,48例患者在肾移植术后采用Pred GsA 骁悉(MMF)免疫抑制剂治疗,就以下方面对两组患者进行观察比较:(1)术后5年内发生排斥反应及临界改变情况;(2)外周血白细胞下降、肝功能异常的发生率;(3)严重感染情况;(4)出现尿蛋白情况;(5)术后5年内肾功能变化情况及移植肾5年存活率.结果:5年内AZa TW组急性排斥反应及临界改变的发生率较MMF组低,分别为11.5%、16.7%和4.8%、6.3%(P＞0.05);GPT高于正常的发生率分别为7.7%、16.6%(P＞0.05);外周血白细胞低于正常的发生率分别为0.96%、18.8%(P＜0.01);严重感染的发生率分别为1.9%、18.8%(P＜0.05),5年内出现蛋白尿的患者例数分别为17.3%、29.2%(P＞0.05),两组移植肾5年存活率相似,分别为89.6%、85.4%(P＞0.05).结论:在肾移植术后应用CsA Pred AZa TW免疫抑制方案是可行的,既可以使肾移植术后急性排斥反应减少,同时还能减少蛋白尿及慢性排斥反应的发生率下降,为国内提高移植肾长期存活率提供了一条新的途径.     

Steroid withdrawal at 3 months after kidney transplantation: a comparison of two tacrolimus-based regimens

The 6 month prospective, randomized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid-resistant acute rejection and with serum creatinine concentrations <160 micromol/l. The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4-6 was low in all groups, both for patients on steroid-free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l (Tac/MMF), and 115.1 micromol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 micromol/l (Tac/MMF/S) and 132.8 micromol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.     

36-month follow-up of 75 renal allograft recipients treated with steroids, tacrolimus, and azathioprine or mycophenolate mofetil

OBJECTIVES: The aim of this retrospective study was to assess the incidence of acute rejection episodes (AR), diabetes mellitus (DM), and serum creatinine (SCr) among renal transplant recipients treated with tacrolimus (Tac), steroids (S), and mycophenolate mofetil (MMF) or azathioprine (Aza). METHODS: Seventy-five renal allograft recipients enrolled in the COSTAMP study were followed for a period of 3 years. Patients were randomized to receive either Tac and MMF (n = 41) or Tac and Aza (n = 34) concomitantly with steroids. Follow-up assessments were performed at 3, 6, 12, 24, and 36 months. RESULTS: Patient survival at month 36 was 91.18% in the Tac/Aza/S group and 97.56% in the Tac/MMF/S group. Graft survival at month 36 was 82.35% and 85.37%, respectively. During the study period, 22 cases of biopsy-proven AR were diagnosed in 17 patients (22.6%). After 36 months the total number of AR was 11 in the Aza-treated group (32.4%) and 11 in the MMF-treated group (26.8%). DM was diagnosed de novo in 17 individuals (22.6%). During 36 months, 10 patients from Aza-treated group (29.4%) and seven from MMF-treated group developed DM (17.1%). Serum creatinine values were not significantly different in both arms of the study. Comparison of arterial blood pressure and total cholesterol revealed no significant changes in any of the studied groups. CONCLUSIONS: We conclude that combinations of steroids, tacrolimus, and azathioprine or MMF provide good results with regard to renal function.     

Conversion from mycophenolate mofetil to azathioprine in renal allograft [corrected] patients within the first month posttransplantation

This retrospective study evaluated the safety of conversion from mycophenolate mofetil (MMF) to azathioprine (Aza) within the first month posttransplantation in 117 renal allograft patients concomittantly treated with cyclosporine (CsA) and prednisone. In 52 Conversion from MMF to Aza was conducted at 2 to 4 weeks posttransplantation in 52 patients (conversion group). Thirty-six patients received MMF (MMF group) and 29 patients were treated with Aza (Aza group). Patients were monitored for allograft function, acute rejection episodes, and CsA levels. The demographics were comparable between groups with respect to age, as well as warm and cold ischemic times of allografts. The cumulative allograft survival rates at 1, 2, 3, and 5 years were 98% +/- 2%, 96% +/- 3%, 90% +/- 4%, 90% +/- 4% in the conversion (n = 52) group versus 79% +/- 7%, 79% +/- 7%, 79% +/- 7%, and 75% +/- 8% in the MMF group (n = 36) versus 93% +/- 5%, 93% +/- 5%, 82% +/- 7%, and 78% +/- 8% in the Aza group (n = 29). The CsA trough levels at 1 year posttransplantation were 208.39 +/- 93.79 ng/mL in the conversion group; 159.30 +/- 52.99 ng/mL in the MMF group; and 241.82 +/- 112.76 ng/mL in the Aza group. The acute rejection rates during a 5-year follow-up were 28.85% in the conversion group; 27.78% in the MMF group; and 24.14% in the Aza group. The rejection-free allograft survival between the conversion group and the MMF group was identical (P < .921). However, allograft survival in the conversion group with acute rejection was significantly higher than the MMF group (P < .024). In conclusion, early conversion from MMF to Aza among renal allograft patients was safe without increased acute allograft rejection during a 5-year follow-up. The overall allograft survival in the conversion group was comparable to patients treated with MMF or Aza therapies.     

HLA-G与肾移植术后急性排斥反应和巨细胞病毒活动性感染的相关性研究

目的 探讨HLA-G的表达水平与肾移植术后急性排斥反应(AR)和巨细胞病毒(CMV)活动性感染的相关性.方法 根据术后是否发生AR或CMV活动性感染,将132例初次肾移植受者分为肾功能稳定组、AR组和CMV组.另选择41例健康供者作为对照组.采用流式细胞术、酶联免疫吸附试验、蛋白质印迹法以及实时定量聚合酶链法检测各组HLA-G及其mRNA的表达,并采用免疫组织化学法观察移植肾组织中HLA-G的表达.结果 肾移植前后各组膜结合型HLA-G1 (mHLA-G1)的表达均处于较低水平,仅术后CMV组mHLA-G1+的中性粒细胞出现显著升高(P＜0.05).术前可溶性HLA-G5(sHLA-G5)的表达水平肾功能稳定组显著高于对照组(P＜0.05);术后sHLA-G5的表达水平CMV组显著高于肾功能稳定组(P＜0.05),而肾功能稳定组均高于对照组和AR组(P＜0.05),AR组与对照组的差异无统计学意义(P＞0.05).术后CMV组sHLA-G5 mRNA的表达水平最高(P＜0.05),肾功能稳定组次之,对照组和AR组均较低.21例AR组移植肾组织活检样本中,17例HLA-G表达呈阴性,3例呈阳性,1例呈弱阳性;9例CMV组移植肾组织活检样本的HLA-G表达均为阳性.132例受者中,28例CMV感染者的AR发生率为7.1％(2/28),104例非CMV感染者的AR发生率为25.0％(26/104),二者间AR发生率的差异有统计学意义(P＜0.05).结论 sHLA-G5可作为预测AR和CMV感染的生物标志分子;CMV感染和AR与受者体内的免疫平衡状况相关.     

Optimization of the immunosuppressive protocol after lung transplantation.

BACKGROUND: The successful use of tacrolimus (Tac)-based immunosuppressive therapy in organ transplantation and our own positive experience in heart transplantation led us to investigate regimens including this agent at our center for lung transplantation. METHODS: From 1991 to 1998, 86 patients underwent lung transplants at our center and 78 of them were included in this analysis. The first 34 patients were treated with cyclosporin (CsA), azathioprine (Aza), and rabbit antilymphocyte globulin; the subsequent 30 patients received Tac with Aza, and the most recent 12 patients Tac with mycophenolate mofetil (MMF). In addition, all patients received prednisone. RESULTS: The number of acute rejection episodes per 100 patient days was 1.5, 0.6, and 0.3 for three treatment groups, respectively. Similarly, the incidence of refractory acute rejection per 100 patient days was lower in both Tac groups (0.20, 0.03, and 0, respectively). Freedom from acute rejection was highest in the Tac-MMF group (P=0.0037 vs. Tac/Aza, P=0.0007 vs. CsA/Aza). Freedom from recurrent acute rejection was significantly higher in both Tac groups (P=0.027 Tac/ Aza vs. CsA/Aza and P=0.025 Tac/MMF vs. CsA/Aza). The incidence of infections per 100 patient days was similar (0.8, 0.5, and 0.8) in all three treatment groups, with a similar distribution of fungal, bacterial, and viral infections. Freedom from infection also showed no difference. The survival rate was significantly higher for the Tac population, with actuarial 1- and 3-year survival rates of 93% and 71%, compared with the CsA group (71% and 51%, respectively, P=0.04). Prevalence of renal dysfunction (creatinine >2.0 mg/ dL) was 18%, 13%, and 0% in the 3 treatment groups, respectively. The development of glucose metabolism disorders was lower in the CsA group than in the Tac-Aza group (15% vs. 27%, P<0.05). CONCLUSIONS: Tac-based immunosuppressive therapy results in a lower rate of acute rejection after pulmonary transplantation, with similar infection rates and a slightly higher incidence of new onset diabetes mellitus compared with CsA-based therapy.