FK506与CsA在肾移植术后抗排斥的临床应用

目的 比较他克莫司(FK506)与环孢素A(CsA)预防肾移植术后排斥反应的效果和安全性。方法 肾移植患者53例分成两组,FK506组为28例,CsA组为25例。其中CsA组因肝功能损害3例,难治性急性排斥反应1例而改换成FK506。FK506起始用0.2mg·kg~(-1)·d~(-1),CsA起始用6mg·kg~(-1)·d~(-1),同时分别联合应用MMF0.75g,每日2次口服,以及术后三天大剂量甲基强的松龙(MP)静滴,第三天改强的松口服,所有病例均严密观察并行血、尿等生化分析。结果 FK506组移植肾功能好,平均7.5天脱酐水平降至平均99.5μmol/L,2例出现排斥反应,经MP连续3d冲击后治愈。CsA组19例移植肾功能良好,6例出现急性排斥,其中3例经MP连续3d冲击后治愈,2例应用OKT3后急性排斥逆转,1例术后3d出现急性排斥经MP与OKT3治疗后改换成FK506,另3例肝损害呈进行性转氨酶升高改换成FK506。FK506组有血糖升高6例(18.8%),高血压5例(15.6％),感染7例(21.9％)。CsA组血糖升高2例(9.5％),高血压5例(23.8％),感染4例(19.0%)。结论肾移植术后应用FK506疗效确切,能有效防治难治性排斥的发生、发展,降低急性排斥的发生率,特别是在乙肝抗原阳性、肝功能受损者比CsA优越。     

肾移植术后应用达利珠单抗62例报告

目的评估达利珠单抗(抗CD25单克隆抗体)诱导治疗后的抗排斥反应疗效。方法对1999年9月～2004年4月间使用达利珠单抗的62例患者进行随访和统计。所有患者均在术中血管开放前1h应用达利珠单抗50mg，术后常规应用激素、环孢素A和霉酚酸酯。根据达利珠单抗的用量分为1剂组、2剂组和大于2剂组。结果随访时间最长达4年9个月，最短3个月。随访期间共发生急性排斥7例(11．3％)，最早1例发生在术后2个月，最晚为术后14个月，平均10．3个月；4例经过激素冲击治疗，完全逆转，2例部分逆转，仅1例发生于术后10个月的排斥，激素冲击治疗无效，术后第13个月移植肾失功而切除。结论应用达利珠单抗诱导治疗，肾移植术后急性排斥发生率降低，并使急性排斥发生时间推迟，程度减轻；可以安全、有效的减少环孢素的剂量。     

霉酚酸酯治疗难治性狼疮性肾炎疗效观察

目的 探讨霉酚酸酯(MMF)治疗难治性狼疮性肾炎(LN)的疗效，以及临床难治性的情况与T细胞亚群改变的关系。方法 LN患者分为两组：治疗组30例，经大剂量激素联合环磷酰胺间断静脉疗法无效或复发者；对照组29例，为随机抽取的同期住院患者，采用流式细胞仪检测两组T细胞亚群。结果 ①LN治疗组症状缓解20例(占66．7％)，部分缓解7例(占23．3％)，有效率占90％；26例伴镜下血尿者中，24例血尿消失；17例伴水肿者中，16例水肿消退；伴高血压14例，12例血压恢复正常，与对照组比较有效率均显著增高(P＜0．05)。②治疗组CD8较治疗前显著降低(P＜0．01)，CD^4 ／CD8^ 显著升高(P＜0．01)；对照组CD3、CD4、CD4^ ／CD8^ 及CD56均无明显差异。结论 MMF治疗难治性LN与经大剂量激素联合环磷酰胺间断静脉疗法相比疗效较好，尤其对控制LN活动期的缓解率高，且有调整T细胞亚群作用。     

肝移植术后糖尿病的诊治策略

目的探讨肝移植术后糖尿病(PTDM)的临床特征和诊治措施。方法回顾性分析我院自2003年10月到2008年8月的58例PTDM患者的临床资料。70.7%(41/58)的患者予胰岛素治疗,激素组23例口服激素的PTDM患者中有15例激素减量或停用;FK506组16例使用单药他克莫司(FK506)免疫抑制方案的PTDM患者,转换为霉酚酸酯(MMF)或西罗莫司(RPM)为主的免疫抑制方案,随访3个月,观察改变免疫抑制方案对PTDM的影响。结果 89.7%(52/58)的PTDM患者临床症状不典型,激素组有5例患者空腹血糖正常,出现糖尿病逆转;11例患者胰岛素用量显著降低或停用,无一例发生急性排斥反应。FK506组有2例患者糖尿病逆转,10例患者胰岛素用量显著降低或停用,1例患者发生急性排斥反应,在FK506加量后排斥反应得以控制。结论肝移植术后PTDM的临床症状不典型,胰岛素治疗占主体。减低激素和FK506用量,转换MMF或RPM为主的免疫抑制方案,可能是防治PTDM的有效手段。     

抗胸腺细胞球蛋白在肾移植中的应用

自1993年6月～1996年2月应用抗胸腺细胞球蛋白（ATG）预防或治疗各种排斥反应86例，结果7例超急性排斥反应者仍有4例再次发生超急性排斥反应，43例术中及术后加用ATG者仅有5例发生急性排斥反应，14例难治性急性排斥反应者有13例得以逆转，17例肾小管坏死者有16例安全度过急性肾小管坏死期，5例慢性排斥反应者肾功能明显好转。认为ATG能有效地预防急性排斥反应，可使绝大多数耐激素难治性急性排斥反应逆转，而且是急性肾小管坏死过渡期最理想的免疫抑制剂，但不能预防超急性排斥反应及慢性排斥反应。所有患者对ATG耐受良好，少数患者可出现一过性白细胞和血小板减少，短期内适量使用ATG不增加患者的感染机会。     

咪唑立宾在临床肾移植中的应用

目的 观察咪唑立宾(MZR)预防肾移植后排斥反应的效果及不良反应.方法 100例肾移植患者后采用由MZR与环孢素A(CsA)、泼尼松(Pred)组成的三联方案预防排斥反应(MZR组),以100例采用CsA.霉酚酸酯(MMF)与Pred组合者为对照(MMF组),随访12个月,观察急性排斥反应发生率,人、肾存活率以及与药物有关的不良反应.结果 术后12个月内,MZR组及MMF组急性排斥反应发生率分别为11%和9%,差异无统计学意义.MZR组人、肾存活率均为100%,MMF组均为99%.MZR组腹泻、严重肺部感染的发生率分别为4%和1%,明显低于MMF组的12%和6%,而血尿酸升高者(25%)明显多于MMF组(6%),差异均有统计学意义(P<0.05).结论 含咪唑立宾的免疫抑制方案用于预防肾移植后的排斥反应安全、有效,不良反应较少.     

肝移植术后急性排斥反应33例诊治报告

目的 探讨肝移植术后发生急性排斥反应的诊断方法与治疗原则.方法 回顾性分析解放军总医院肝胆外科2007年1月-2010年12月收治的232例肝移植患者的临床资料,对术后33例发生急性排斥反应患者的诊断及治疗方法进行分析.结果 42例患者术后因肝功能异常而行肝脏活检并根据Banff标准诊断,其中33例发生急性排斥反应,28例为单次,5例为两次,急性排斥反应发病率为14.2％.发生急性排斥反应的患者经激素冲击或调整免疫抑制药物剂量后,31例缓解,2例死亡.结论 肝脏穿刺活检对于肝移植术后急性排斥反应的诊断有重要意义,免疫抑制药物剂量调整以及激素冲击是治疗急性排斥反应的有效措施.     

肾移植术后患者应用西罗莫司对他克莫司剂量的影响

目的观察肾移植术后联合应用西罗莫司(雷帕霉素)对他克莫司(FK506)剂量的影响。方法60例肾移植术后患者随机分为两组,研究组30例,免疫抑制方案采用西罗莫司+他克莫司+泼尼松;对照组30例,采用麦考酚吗乙酯(MMF)+他克莫司+泼尼松联合治疗。术后随访2年,比较两组的人、肾存活率,急性排斥反应率,他克莫司用量,肾功能变化和不良事件发生率。结果研究组、对照组全部如期完成观察,两组的人肾存活率均为100%,研究组、对照组急性排斥反应发生率分别为7%(2/30)、10%(3/30),经肾上腺皮质激素(激素)冲击治疗后逆转;研究组在维持他克莫司血药浓度与对照组相当情况下,其用量低于对照组,比较差异有统计学意义(P0.05)。两组的不良事件发生率相近(60%比70%,P0.05)。结论联合西罗莫司+他克莫司+泼尼松方案用作肾移植术后免疫抑制治疗是安全有效的,且能减少他克莫司的剂量。     

霉酚酸酯预防肾移植术后近期急性排斥反应的观察

目的 :观察霉酚酸酯 (MMF)在预防肾移植术后近期 (3个月 )急性排斥反应 (AR)的情况。方法 :将 112例患者随机分成 2组 ,MMF(2 .0 g/d)组和硫唑嘌呤 (Aza)组。两组患者均同时接受相似剂量的环孢素 A和类固醇激素治疗。结果 :观察 3个月 ,MMF组 6 0例 ,AR发生率为 16 .7% (10 /6 0 ) ,Aza组 5 2例 ,AR发生率为 42 .3%(2 2 /5 2 ) ,两组差异有极显著意义 (P <0 .0 1)。 MMF组 5例出现血白细胞、血小板等不同程度下降 ,3例出现腹泻 ,在 MMF减量或停药后均恢复正常 ,未见有 MMF引起的肝、肾功能异常病例 ;Aza组有 9例出现肝功能损害。结论 :MMF具有预防和减少肾移植术后近期 AR效果 ,MMF的安全性可靠 ,副作用轻且为可逆性。     

霉酚酸酯与环磷酰胺治疗难治性肾病综合征的对照观察

目的比较霉酚酸酯（MMF）和间断环磷酰胺（CTX）静脉疗法对难治性肾病综合征的疗效及安全性。方法将2000年1月至2007年10月间在我院诊断的30例难治性肾病综合征患者分为激素联合MMF治疗组（MMF组,n=14）、激素联合CTX间断静脉冲击治疗组（CTX组,n=16）。MMF剂量1．5～2．0g／d,CTX剂量0．75～1．00g／m^2,每个月1次,共6次,每3个月1次,共2次。比较2组治疗12个月的临床缓解率和相关临床指标变化。结果①2组治疗后尿蛋白、血脂水平明显下降,血清白蛋白显著上升,血肌酐无明显改变。②治疗6和12个月时MMF组总缓解率高于CTX组。③不良反应：MMF组并发带状疱疹和白细胞减少各1例,CTX组有2例出现明显消化道症状,2组各有1例并发带状疱疹、细菌性肺炎、白细胞下降、天冬酸氨基转移酶升高、脱发。结论激素联合MMF治疗难治性肾病综合征缓解率高于CTX静脉冲击疗法,能更有效改善蛋白尿。MMF不良反应发生率低于CTX疗法。     

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。     

Single centre experience with mycophenolate mofetil for refractory rejection in cadaveric renal transplantation

Ten patients with refractory rejection following renal transplantation were treated with mycophenolate mofetil (MMF) in an attempt to salvage the allografts. All cases of rejection were biopsy-proven. Seven of the patients had initially been on tacrolimus-based triple therapy and three were on cyclosporin-based regimens. Those on cyclosporin had been unsuccessfully converted to tacrolimus prior to receiving MMF. All patients had received at least one course of methylprednisolone pulse therapy and three had been given OKT3 prior to MMF. MMF was prescribed at a dose of 2000 mg per day in two divided doses and was given in addition to tacrolimus and prednisolone. Eight of the ten patients showed evidence of reversal of rejection, as indicated by improvement in renal function following commencement on MMF, whilst two patients experienced ongoing rejection and underwent graft nephrectomy. One of the patients successfully treated has since had his MMF discontinued due to gastrointestinal intolerance. We conclude that MMF is effective in salvaging renal allografts with resistant rejection and that it has an acceptable side-effect profile. Received: 30 September 1997 Received after revision: 2 December 1997 Accepted: 14 January 1998     

Late developing C4d-positive humoral renal allograft rejection associated with withdrawal of mycophenolate mofetil

In renal transplantation, C4d-positive acute humoral rejection (AHR) usually develops in the early stage posttransplantation. It is clear C4d can be detected late after the operation, when it is associated with chronic renal allograft rejection. We report a case of a renal allograft recipient who experienced C4d-positive acute renal allograft rejection associated with withdrawal of mycophenolate mofetil (MMF) at 10 months after transplantation. This 21-year-old single male patient received his first cadaveric renal allograft under immunosuppression with cyclosporine, MMF, and prednisolone. The serum creatinine recovered to the normal range within 4 days. A protocol biopsy performed at 1 month after transplantation revealed no signs of rejection. The graft function was stable until 10 months postoperation, when MMF was converted to mizoribin. Three days later a biopsy showed a C4d-positive rejection. Patient had no response to the MMF combined with tacrolimus and steroid bolus therapy, which generally improves 85% of AHR among Chinese. He finally returned to dialysis. Our report suggested that C4d positive AHR may occur late after transplantation. MMF is important to suppress the body's humoral response to allograft; when MMF was converted to a weaker immunosuppressant, the dose of the other immunosuppressants (cyclosporine for example) must be adjusted properly.     

Mycophenolic acid dose reductions result in poor long-term renal allograft survival: comparison between mycophenolate sodium and mycophenolate mofetil

Mycophenolate acid (MPA) therapy is associated with a decrease in acute rejection rates and excellent renal allograft survival. Unfortunately, mycophenolate mofetil (MMF) is associated with significant adverse effects (AE), which, in many cases, preclude full-dose therapy. Previously, lower MMF drug exposure was significantly associated with a greater risk of rejection. Patients who had a ≥50% dose reduction of MMF experienced a lower graft survival compared to those who tolerated full-dose MMF. Mycophenolate sodium (MPS) was designed to lessen MPA-associated AE. In this retrospective study, we studied the tolerability and long-term outcomes in renal transplant recipients (RTR) treated with MPS versus MMF. Four hundred forty-nine RTRs who received MPS or MMF for more than 3 months were classified into three groups: group 1: MMF-treated; group 2: MPS-treated; and group 3; patients who converted from MMF to MPS due to AE. Donor and recipient demographics as well as induction and maintenance immunosuppressive therapies were similar in all groups. Patient survival was not different in all groups. However, long-term graft survival was lower in patients whose dose of either MPS or MMF was reduced by ≥50%. Moreover, a ≥50% MPA dose reduction was associated with a higher rate of rejection compared to full dose (38% vs 21%, respectively, P < .01). Compared to patients treated initially with MMF, fewer MPS-treated recipients required dose reductions (65% vs 42%, respectively, P < .001). Furthermore, 38% of patients in group 3 tolerated full-dose MPS despite previous intolerance to MMF. Finally, the long-term graft survival was best in MPS-treated RTR and worst in those who converted from MMF to MPS due to AE. We conclude that MPS is better tolerated than MMF, which may explain the superior graft outcome in RTR who were treated with MPS from the onset.     

Conversion to enteric-coated mycophenolate sodium from various doses of mycophenolate mofetil: results of a prospective international multicenter trial in maintenance renal transplant patients receiving cyclosporine

Conversion from mycophenolate mofetil (MMF, CellCept) to enteric-coated mycophenolate sodium (EC-MPS, myfortic) is safe and effective in renal transplant patients treated with the standard dose of 2 g MMF. In this 6-month, international, multicenter, open-label, single-arm trial, a large cohort of maintenance renal transplant patients receiving different doses of MMF were converted under normal clinical conditions to equimolar doses of EC-MPS. Mean calculated creatinine clearance remained stable from the time of study entry (59.6 +/- 19.7 mL/min) to the end of the study (58.3 +/- 19.8 mL/min). Adverse events were reported by 152 patients (67%), with gastrointestinal complications being observed in 45 patients (20%). Thirty-three patients (15%) experienced adverse events or infections with a suspected relation to EC-MPS, including one case of anemia and two cases of leukopenia. Eleven patients (4.9%) required a reduction in EC-MPS dose and seven patients (3.1%) permanently discontinued EC-MPS owing to adverse events. At month 6 after conversion, five patients (2.2%) experienced biopsy-proven acute rejection. There were no graft losses or deaths. These data support earlier findings that stable maintenance renal transplant patients receiving MMF with cyclosporine with or without corticosteroids can be converted to EC-MPS with no compromise in efficacy and tolerability, and no adverse effect on renal function.     

Mycophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation

Mycophenolate mofetil (MMF) significantly decreases acute rejection rates after renal transplantation, but intolerance often occurs, leading to dose reduction. The clinical effect of MMF dose reduction has not been clearly established. This study determined whether MMF dose reduction after renal transplantation was associated with subsequent risk of acute rejection. This retrospective cohort study assessed 213 renal transplant recipients. Cox regression was used to model MMF dose as a time-dependent variable, with time to first acute rejection as the primary outcome. One hundred twenty-six patients (59%) had a total of 176 MMF dose reductions during the study. MMF dose was reduced because of leukopenia (55.1%), gastrointestinal symptoms (22.2%), infection (7.4%), malignancy (1.1%), and unknown reasons (14.2%). The cumulative number of days with the MMF dose reduced below full dose was an independent predictor of acute rejection. The relative risk of rejection increased by 4% for every week that the MMF dose was reduced below full dose. No significant association was observed between the number of days with MMF dropped below full dose and allograft failure. The cumulative number of days with the MMF dose dropped below full dose is a significant predictor of acute rejection after renal transplantation. Clinicians need to be aware of the rejection risk when the MMF dose is reduced and maintain close surveillance on such patients.     

Comparative study of clinical outcome in kidney transplantation between early steroid withdrawal protocol using basiliximab, calcineurin inhibitor, and mycophenolate mofetil and triple regimen consisting of calcineurin inhibitor, mycophenolate mofetil, and steroid

AIMS: Effect of early steroid withdrawal protocol using basiliximab in kidney transplantation (KTx) on the clinical outcomes was investigated as compared with triple regimen. METHODS: Kidney transplant patients in group 1 (n = 62) were treated with 8 mg/kg of cyclosporine (CsA), 2000 mg of MMF, two bolus IV injections of 20 mg of basiliximab and 500 mg of methylprednisolone (MP) rapidly tapered and withdrawn at 14 postoperative days (POD). Group 2 (n = 56) was treated with same dose of CsA and MMF, and 250 mg of MP tapered and continued. Acute rejection (AR) episodes were treated with MP pulse therapy followed by muromonab CD3 (OKT3) in case of steroid-resistant rejection. RESULTS: In 46 of 62 cases (74.2%) in group 1, steroid was successfully withdrawn at 13.7 +/- 1.7 POD. Graft survival at 3, 6, and 12 months in group 1 was 100%, 100%, and 98.4% (one death with functioning graft), and 100%, 98.2%, and 96.4% in group 2, respectively. The incidence of AR was 12.9% for group 1 and 42.9% for group 2, among which 21 cases in group 2 were treated with ALG or OKT3; no patient needed ALG or OKT3 in group 1. Fifteen cases in group 1 and 13 cases in group 2 developed CMV antigenemia, among which febrile episode was exhibited in 3 cases (4.8%) in group 1 and 5 cases (8.9%) in group 2. CONCLUSIONS: Early steroid withdrawal protocol using basiliximab is promising for reducing the incidence of AR (especially steroid-resistant rejection), CMV diseases, and steroid-related complications.     

Sirolimus rescue therapy for refractory rejection in renal transplantation.

BACKGROUND: Acute renal allograft rejection episodes refractory to antilymphocyte preparations almost inevitably progress to transplantation loss. To reverse ongoing rejection processes, we administered sirolimus (RAPA) after failure of conventional immunosuppressive regimens including full courses of antilymphocyte sera. METHODS: All 36 renal transplantation recipients reported herein displayed either Grade IIB or Grade III biopsy-proven (Banff 1993 criteria) ongoing rejection episodes despite prior treatment with pulse and/or oral recycling of steroids and at least one 14- to 21-day course of murine (OKT3) or equine (ATGAM) antilymphocyte treatment. We compared the actual 12-month outcomes of two demographically similar cohorts of patients treated for refractory rejection with RAPA (Group I; n=24) or mycophenolate mofetil (MMF; Group II; n=12) added to a baseline regimen of cyclosporine (CsA)/prednisone (Pred). RESULTS: Rescue therapy reversed the renal dysfunction in 96% of patients in the RAPA group versus 67% in the MMF group (P=0.03) despite the fact that a greater fraction of patients in the RAPA (17 of 24) than the MMF group (6 of 12) had experienced two or more episodes of acute rejection before study entry and the fact that the recurrent bouts of acute rejection occurred within the first 6 months posttransplant in 94% of patients in the RAPA group compared with 50% (P=0.005) in the MMF group. Among the patients who were reversed successfully, the rates of rebound acute rejection were similar (4% vs. 8%). The mean serum creatinine values were slightly, although not significantly, lower among RAPA than MMF patients at 1, 3, 6, and 12 months: namely, 2.6 vs. 2.8, 2.8 vs. 3.2, 3.0 vs. 3.3, and 2.8 vs. 3.2 mg/dL, respectively. The 1-year patient and graft survival rates were similar: namely, 88% vs. 92% and 83% vs. 67% for the RAPA versus MMF groups. CONCLUSION: RAPA is a potent immunosuppressive agent for the treatment of refractory renal allograft rejection.     

Randomised open clinical trial of conversion from mycophenolate mofetil to azathioprine in cadaveric renal transplantation

Abstract Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The search for a less expensive immunosuppressive protocol has led to an open randomised clinical trial of conversion from MMF to azathioprine (Aza). A total of 28 renal allograft recipients treated with prednisone, cyclosporine, and MMF was randomised into two groups: converted (early conversion) and control (late conversion). Conversion from MMF to Aza was conducted at the end of the 4th post‐transplant month in the converted group and after the 12th month in the control. During the 20‐month observation period, biopsy‐proven acute rejection occurred more frequently in the converted than in the control group, although the difference was not statistically significant. Early conversion from MMF to Aza increased the risk of subsequent rejection in those patients who underwent at least one episode of acute rejection prior to conversion.