低剂量吗替麦考酚酯在直系亲属活体肾移植中的应用

近年来,国内亲属活体肾移植呈明显上升趋势,鉴于供受体之间良好的组织相容性、排斥反应也相对较少,有学者提出适当减少免疫抑制剂剂量,但目前对此尚无一致及具体的方案。为了探讨低剂量的免疫抑制剂方案应用的可行性,使活体肾移植技术更加安全、经济,对厦门大学附属东南医院具有直系血缘关系、亲属活体肾移植患者56例,活体肾移植后2周起实施低剂量吗替麦考酚酯分散片的免疫抑制方案,人/肾存活率分别均为96.4%(54/56)和98.2%（55/56）。排斥反应5例,其中2例为移植后2周内发生。肺部感染2例、带状疱疹1例、水痘1例,贫血1例、腹泻3例。结果证明应用该治疗方案疗效满意,排斥反应发生率并无增加、而肺部感染等并发症明显减少,而且节省了费用。     

亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的应用

背景：亲属活体肾移植供、受者移植前准备充分,供肾热、冷缺血时间较短,HLA配型的组织相容性好,移植后排斥反应发生率低,为亲属活体供肾肾移植后采用低剂量免疫抑制剂方案提供了可能性。 目的：探讨亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的安全性和有效性。 方法：选取2006-01/2008-06在南京医科大学第一附属医院肾移植中心行亲属活体供肾移植的受者38例,移植后常规使用环孢素A/他克莫司+吗替麦考酚酯+泼尼松的三联免疫抑制方案。将38例患者随机分为两组：CNI常规剂量组(n=18),移植后初始药物剂量为环孢素A 6 mg/(kg•d)或他克莫司0.12 mg/(kg•d);CNI低剂量组(n=20),术后初始药物剂量为环孢素A 4 mg/(kg•d)或他克莫司0.08 mg/(kg•d);两组吗替麦考酚酯和泼尼松使用剂量相同。移植后密切随访,比较两组患者移植后不同时期的肾功能以及急性排斥反应、肺部感染、肝功能损害、肾毒性等并发症的发生情况。 结果与结论：随访12个月,CNI常规剂量组重度肺部感染死亡1例,CNI低剂量组无死亡病例。两组移植肾功能及急性排斥反应发生率比较差异均无显著性意义(P > 0.05);CNI低剂量组肝功能损害、钙调蛋白酶抑制剂肾毒性发生率显著低于CNI常规剂量组 (P < 0.05)。此外,采用低剂量钙调蛋白酶抑制剂免疫抑制方案明显减轻了亲属肾移植患者的经济负担。说明亲属活体供肾移植后采用低剂量钙调蛋白酶抑制剂的免疫抑制剂方案安全、有效。     

他克莫司和环孢素A对肾移植后患者炎性细胞因子和血脂的影响

背景：环孢素A与他克莫司是肾移植后临床广泛应用的免疫抑制剂。 目的：观察他克莫司和环孢素A对肾移植后炎性细胞因子和血脂的影响。 方法：选择首次接受同种异体肾移植后患者112例,随机分为环孢素A组和他克莫司组,移植后分别给予环孢素A+吗替麦考酚酯+糖皮质激素三联疗法与他克莫司+吗替麦考酚酯+糖皮质激素三联疗法。 结果与结论：他克莫司组的1年人/肾存活率、治疗逆转率高于环孢素A组(P < 0.05),急性排斥反应发生率低于环孢素A组(P < 0.05);移植后1个月及1年的血清白细胞介素2,6,8和血糖水平高于移植前(P < 0.05),低于环孢素A组(P < 0.05),血清白细胞介素4,10低于移植前(P < 0.05),高于环孢素A组(P < 0.05);移植后1个月的血清总胆固醇、三酰甘油和低密度脂蛋白胆固醇高于移植前(P < 0.05),但低于环孢素A组(P < 0.05);移植后1年的血清总胆固醇和低密度脂蛋白胆固醇低于环孢素A组(P < 0.05)。说明他克莫司可通过抑制肾移植后炎性细胞因子释放,改善糖脂代谢等途径降低患者的排斥反应,提高肾移植的存活率。     

吗替麦考酚酯在自身免疫疾病中的临床应用

吗替麦考酚酯(MMF)是一种新型抗代谢类免疫抑制药,其有效成分为吗替麦考酚酸(MPA).MMF可选择性地抑制T、B淋巴细胞中嘌呤的合成进而抑制细胞增殖.研究发现MMF可有效治疗自身免疫性疾病.此文主要介绍MMF在自身免疫疾病中的临床应用,并特别关注此药应用于重症肌无力患者的研究情况.     

环孢素A和他克莫司对肾移植受者血脂的影响

背景：高血脂为肾移植后常见的并发症,常用的免疫抑制剂包括环孢素A,泼尼松和他克莫司都会对患者血脂产生影响。 目的：探讨他克莫司与环孢素对肾移植术后患者血脂的影响。 方法：按照不同的服药方案将肾移植后的患者随机分成2组：环孢素A组(n=20),免疫抑制剂方案为环孢素A+麦考酚酸莫酯+泼尼松;他克莫司组(n=23),免疫抑制剂方案为他克莫司+麦考酚酸莫酯+泼尼松。于移植前,移植后1个月及6个月对患者抽血化验,观察两组患者总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇的变化。 结果与结论：两组各项指标移植前后比较均有差异,两组间比较,移植后1个月和6个月总胆固醇和低密度脂蛋白胆固醇差异显著(P < 0.05);高密度脂蛋白胆固醇和三酰甘油之间差异不显著。结果表明：对肾移植后肾功能稳定的患者实施以环孢素A为免疫抑制剂的方案,三酰甘油和低密度脂蛋白胆固醇更易升高,他克莫司在脂类代谢方面表现出更少的不良反应。与环孢素A相比,肾移植后患者应用他克莫司高脂血症的发病率明显降低。     

同一移植中心2年间亲属活体肾移植38例安全性评估

背景：国内活体器官供者的安全性令人关注,供者移植后并发症,受者移植效果不理想或失败的病例有所发生。因此,必须重视活体肾移植,保证供者的生命安全和生活质量。 目的：探讨亲属活体肾移植的安全性。 方法：回顾性分析38对亲属活体肾移植供受者的临床资料,总结治疗经验。38例供者移植前明确身份,完善检查,充分告知治疗方案,合理手术。38例受者移植前充分透析,改善全身状况后行肾移植,移植后给予他克莫司或环孢素A、霉酚酸酯、皮质激素的三联基础免疫抑制方案治疗。观察肾移植后供受者肾功能变化、并发症发生率,以及受者急性排斥反应发生情况。 结果与结论：亲属活体肾移植等待时间短、花费较少、长期存活率高的优势是明显的,供者的近期和远期风险都很小。尽管如此,进行亲属活体肾移植仍要充分评估供受者的风险,保证供受者的安全。     

肾移植后他克莫司与五酯胶囊合用致高血钾症1例

背景：肾移植患者由于免疫抑制剂的药物肝毒性,肝功能异常发生率高,对临床出现肝功能异常者,需护肝治疗。但合用护肝药必须监测免疫抑制剂浓度。 目的：探讨肾移植患者他克莫司与五酯胶囊合用对他克莫司浓度及血生化的的影响。 方法：回顾性分析1例以他克莫司为免疫抑制剂的肾移植患者加服及停用五酯胶囊时他克莫司浓度及肾功能、血生化变化。患者因“慢性肾小球肾炎,慢性肾功能不全”于1998-06起行血液透析治疗。2000-08行同种异体尸体肾移植,移植后免服他克莫司+吗替麦考酚酯+泼尼松。移植后4个月患者出现肝功能异常,加用联苯双酯。2010-07-25患者停用联苯双酯,改服五酯胶囊。2010-07-29患者停用五酯胶囊。 结果与结论：服用他克莫司的肾移植受者,合用五酯胶囊,他克莫司血浓度显著升高。由5.3 ng/L升至24.7 ng/L,并合并高血钾症,停用五酯胶囊1周,他克莫司浓度由24.7 ng/L降至6.1 ng/L,血钾由6.4 mmol/L降至4.6 mmol/L。提示移植肾功能稳定的肾移植受者,在加用五酯胶囊,必须严密监测他克莫司血浓度及肝肾功能、电解质,及时调整他克莫司用量,保护移植肾功能。     

人类白细胞抗原配型及其抗体监测在亲属活体供肾移植中的应用

背景：人类白细胞抗原(HLA)配型是影响肾移植效果的重要因素，其抗体检测有助于筛查术前致敏者。 目的：探讨人类白细胞抗原配型联合抗人类白细胞抗原抗体监测在亲属活体供肾移植中的应用价值。 设计、时间及地点：单一样本观察，病例回顾性分析，于2004-02/2007-09在中山大学附属第一医院完成。 对象：选择同期中山大学附属第一医院行亲属活体供肾者、首次肾移植者66例，供者男27例，女39例，年龄19~66岁；受者男50例，女16例。 方法：采用序列特异性引物聚合酶链反应法测定拟行亲属活体肾移植的供、受者人类白细胞抗原A，B，DR抗原分型，采用补体依赖微量细胞毒性试验于术前行交叉配型。采用甲泼尼龙联合抗CD25单克隆抗体或抗胸腺细胞球蛋白于术中和术后早期作免疫诱导治疗，采用以环孢素A或他克莫司为主联合吗替麦考酚酯和泼尼松的三联方案作维持性免疫抑制治疗。 主要观察指标：采用酶联免疫吸附法筛查和监测受体的群体反应性抗体；检测肾移植效果及不同免疫抑制方案患者急性排斥情况。 结果：66例亲属活体供肾移植中，供受者人类白细胞抗原A，B，DR配型错配数分别为0~3个60例，4~6个6例。在0~3 错配数受体中，术后3例(5%)发生移植肾功能延迟恢复，4例(7%)发生急性排斥。在4~6错配数受体中，术后1例(17%)移植肾功能延迟恢复、2例(33%)急性排斥。人类白细胞抗原0~3 错配数和4~6 错配数两组比较，其移植肾功能延迟恢复和急性排斥发生率差异均有显著性意义(P < 0.05)。不同免疫抑制治疗方案对移植肾功能延迟恢复和急性排斥发生率无显著影响(P > 0.05)。所有急性排斥患者经甲泼尼龙和/或抗胸腺细胞球蛋白等治疗后逆转。对3例术前预致敏受者术后定期监测群体反应性抗体变化：1例群体反应性抗体水平无明显变化，移植肾功能顺利恢复；2例术前经血浆置换后转阴或自然转阴，术后发生急性排斥，经甲泼尼龙、抗胸腺细胞球蛋白等治疗后逆转。 结论：亲属活体供肾组织配型中，人类白细胞抗原配型与肾移植术后急性排斥、移植肾功能延迟恢复等相关。术前组织配型及抗人类白细胞抗原抗体动态监测对于亲属活体供肾移植特别是预致敏受者很重要。     

吗替麦考酚酯对大鼠弥漫性轴索损伤后脑干胶质细胞激活及硫酸软骨素表达的影响简

目的探讨吗替麦考酚酯（MMF）对大鼠弥漫性轴索损伤（DAD后脑干胶质细胞激活及硫酸软骨素表达的影响。方法将72只DAI后SD大鼠随机分为3组：空白对照组、生理盐水治疗组（NS组）、吗替麦考酚酯治疗组（MMF组）。MMF组腹腔注射MMF（100mg／kg）干预;NS组腹腔注射等量生理盐水;空白对照组只作针扎刺激,不注射任何药物。伤后7、14、28d处死3组大鼠,取大鼠脑干进行巨噬细胞一小胶质细胞质抗原（ED-1）、胶质纤维酸性蛋白（GFAP）和硫酸软骨素（CS）免疫组化染色,检测活化小胶质细胞、活化星形胶质细胞、硫酸软骨素蛋白聚糖,并以累积光密度（IOD）值进行定量评估。结果在伤后不同时间点,MMF组活化小胶质细胞、活化星形胶质细胞、硫酸软骨素蛋白聚糖IOD值均显著低于NS组与空白对照组（P〈0．05）;而Ns组和空白对照组之间无统计学差异（P〉0．05）。结论MMF可抑制大鼠DAI后脑干小胶质细胞和星形胶质细胞激活,还可降低cs表达。     

夫妻活体供肾移植与血缘亲属供肾移植

背景：夫妻间活体肾移植尽管在组织配型方面差于血缘关系供肾移植,但在临床实践观察中夫妻肾移植与血缘关系肾移植间近期疗效并无明显差异。 目的：对比同期实施的夫妻活体供肾移植和血缘亲属供肾移植的临床疗效,总结夫妻活体供肾移植的临床经验。 方法：回顾性分析郑州人民医院实施的夫妻活体供肾移植18例及血缘亲属供肾移植100例的临床资料,通过对两组移植前组织配型情况和移植后(1,3,6个月)肾功能恢复情况,移植肾功能延迟恢及半年内急性排斥反应发生率、感染发生率等指标的分析,对夫妻活体供肾移植和血缘亲属供肾移植的临床疗效进行比较。 结果与结论：同期进行的18例夫妻活体供肾移植组织配型情况较血缘关属供肾移植患者情况差。在移植方案及免疫抑制治疗方案相同的情况下,夫妻活体供肾移植后6个月内血肌酐恢复情况、术后移植肾功能延迟恢、急性排斥反应发生率、感染发生率,均与同期进行的血缘亲属活体供肾移植差异无显著性意义(P > 0.05)。结果表明,无血缘关系的夫妻间供肾移植与血缘亲属供肾移植治疗效果相近。     

Mycophenolate mofetil in multiple sclerosis

OBJECTIVE: To describe experience with the use of mycophenolate mofetil (MMF) in the treatment of multiple sclerosis (MS). BACKGROUND: MMF is a potent immunosuppressant that is a selective inhibitor of inosine 5'-monophosphate dehydrogenase type II, the enzyme responsible for the de novo synthesis of the purine nucleotide guanine within activated T and B lymphocytes and macrophages. METHODS: A retrospective review of experience in treating 79 MS patients with MMF (61 with secondary progressive, 14 with relapsing-remitting, and 4 with primary progressive MS) in the authors' MS center. RESULTS: In most cases, MMF was added as adjunctive therapy in patients already being treated with either interferon-beta (n = 44) or glatiramer acetate (n = 20). Fifteen patients not able to use interferon or glatiramer acetate were treated with MMF monotherapy. Seventy percent of the patients continued MMF therapy. Eight patients discontinued therapy because of side effects, 7 patients continued to exhibit evidence of disease progression, 4 were denied insurance coverage, 2 were lost to follow-up, and 1 patient had an elevation of hepatic transaminases that resolved on discontinuation of MMF. One patient discontinued MMF therapy secondary to cytomegalovirus diarrhea. CONCLUSION: MMF was well tolerated by the majority of patients treated. While these clinical observations were uncontrolled, the clinical course of MS was either unchanged or subjectively improved in many of the treated patients. A randomized controlled trial of MMF in MS, either as monotherapy or in conjunction with interferon or glatiramer acetate, appears warranted.     

Mycophenolate mofetil for ocular myasthenia

Objective To study the safety and tolerability of mycophenolate mofetil (MM), since this steroid-sparing immunomodulatory agent with less side effects, compared to corticosteroids, may be considered for long-term management of ocular myasthenia (OMG). Methods Consecutive patients with OMG started on MM between December 2000 and December 2002 were followed up to December 2006. Results All of the 31 patients with OMG were treated with prednisone at 40–60 mg/d while MM was increased up to the target of 1.0 g/d. After symptoms completely resolved, all patients were then tapered off prednisone over a period of 4 weeks. Eightyseven percent (27/31) of patients continued on MM during the study. Mycophenolate mofetil discontinuation occurred in 4/31 (13%) of patients within the first four months of starting the drug. Of the patients who continued on MM, 93% (25/27) remained at stage I of the disease. The 7% (2/27) of patients on MM who generalized in our study did so by 2 years and were treated with additional prednisone. MM-related adverse events included nausea in 9 of 31 patients, diarrhea in 5 of 31 patients, and vomiting in 1/31 patients. No cases of infections, cytopenias, or malignancies were observed. Conclusions Eighty-seven percent of OMG patients on corticosteroids who were switched to MM remained at Stage I of the disease over a mean period of 4.2 years. MM at 1.0 g/d was safe and tolerable as a long-term immunosuppressant for OMG.     

Mycophenolate in treatment-resistant inflammatory neuropathies

There has been an increasing interest in the use of mycophenolate as an immunomodulatory drug in neuromuscular diseases. We report five consecutive patients with treatment-resistant chronic inflammatory demyelinating polyradiculoneuropathy or multifocal motor neuropathy who were treated with mycophenolate. None showed clinically significant benefit. The use of mycophenolate did not result in the reduction in the dose of corticosteroid or other immunosuppressive agents in any patient. Side-effects, although not serious, were troubling enough for two patients to stop mycophenolate.     

Mycophenolate mofetil in the therapy of severe myasthenia gravis

Mycophenolate mofetil is a novel immunosuppressive drug already established in transplantation medicine. Recently, results of three open clinical trials on mycophenolate mofetil in myasthenia gravis have been reported. Mycophenolate mofetil in a dose of 1.0-2.0 g/day was given in 2 patients with severe refractory myasthenia gravis and in 1 patient with myasthenia gravis-polymyositis syndrome. Apart from dose-dependent reversible hemolytic anemia in 1 patient, no severe side effects occurred. Considerable improvement of myasthenic symptoms was seen in all patients within 3-6 months after the initiation of this therapy. Mycophenolate mofetil may be considered as a useful alternative in the treatment of severe myasthenia gravis when standard therapeutic regimens fail. It is usually well tolerated and its application is simple.     

Mycophenolate mofetil for myasthenia gravis: an open-label pilot study

In an open-label study, 12 patients with refractory MG or who were taking only corticosteroids and required additional immunosuppression received mycophenolate mofetil 1 g twice daily for 6 months. A reduction of three points in a quantified MG score and two points in a manual muscle test or a reduction of 50% in corticosteroid dose defined efficacy. Eight patients improved, beginning after 2 weeks to 2 months. No major side effects were observed.     

Mycophenolate mofetil-induced pseudotumor cerebri in a boy with autoimmune lymphoproliferative disease

Introduction  

Pseudotumor cerebri (PTC) is a syndrome characterized with increased intracranial pressure, normal cerebrospinal fluid content (CSF), and a normal brain on imaging studies. In this case report, PTC has been linked to mycophenolate mofetil (MMF) that has been used for autoimmune lymphoproliferative syndrome (ALPS).     

Mycophenolate mofetil and tacrolimus: new therapeutic options in neuroimmunological diseases

Mycophenolate mofetil (MMF) and tacrolimus are novel immunosuppressive drugs, both first established in transplantation medicine and now used increasingly in neuroimmunological diseases including myasthenia gravis, dysimmune polyneuropathies, and myositis. In myasthenia gravis, the efficacy and safety of MMF has been shown by one open-label trial; one small, double-blind, placebo-controlled trial; and a few retrospective analyses. Similarly, for tacrolimus the greatest experience and evidence for efficacy and safety have been gathered in myasthenia gravis. MMF and tacrolimus have both been used as an alternative treatment for various other autoimmune diseases in which azathioprine or cyclosporine were not sufficiently effective. However, experience with tacrolimus in dysimmune polyneuropathies and myositis is limited. At this time, the available data suggest that MMF and tacrolimus are well suited for long-term immunosuppression in patients with myasthenia gravis. The spectrum of neuroimmunological diseases in which these drugs may be used has not been finally delineated and will require further controlled studies.