吗替麦考酚酯与麦考酚钠肠溶片对肾移植受体血药浓度的影响

目的  探讨吗替麦考酚酯（MMF）与麦考酚钠肠溶片（EC-MPS）在同等生物效应剂量下对肾移植受体麦考酚酸（MPA）血药浓度和不良反应的影响。方法  回顾性分析106例活体供肾移植受体的临床资料。按肾移植术后服用不同药物分为两组,MMF组（M1组,62例）和EC-MPS组（M2组,44例）。两组受体的免疫抑制方案分别为M1组用他克莫司（FK506）+MMF+泼尼松,M2组用FK506+EC-MPS+泼尼松。分析两组受体服药后1、2、3周和1、2、3个月MPA血药浓度的变化情况、不良反应发生情况及服用药物所花费用。结果  采取同等生物效应给药,服药后第1、2、3周,第1、2、3个月时M1组MPA血药谷浓度比M2组低,各个时间点两组间比较,差异均有统计学意义（均为P < 0.05）。与M1组比较,M2组术后不良反应的发生率较低且症状较轻。采用同等生物学效应给药,M1组服用MMF所花费用1 710元/月,M2组服用EC-MPS所花费用2 736元/月,但M1组因治疗药物不良反应所产生费用远高于M2组。结论  同等的生物效应剂量下服用EC-MPS的患者相对服用MMF的患者能维持更高的MPA血药浓度并且不良反应更少。     

心脏移植后吗替麦考酚酯的个体化应用

目的 比较心脏移植术后吗替麦考酚酯(MMF)个体化给药方案与固定给药方案的临床疗效,总结基于血霉酚酸(MPA)浓度监测的MMF个体化方案应用经验.方法 研究组48例受者为2010年1月至2011年12月间接受心脏移植术,术后依据临床事件及血MPA浓度谷值(MPA-C0)进行个体化MMF剂量调整,MPA-G0目标浓度为2.0～4.0 mg/L,随访12个月;对照组从数据库中选取2007年1月至2009年12月行心脏移植手术,并且与研究组配对同质程度较高的55例受者,术后服用固定剂量MMF,如有不良事件发生则经验性调整剂量,回顾术后12个月内的随访数据.记录并比较二组间服药量、急性排斥反应发生率及MMF相关不良反应发生率.结果 研究组术后12个月随访率95.8％,MMF用药1周后首次检测MPA-AUC0-12为(54.37±17.03)mg·h·L-1,MPA-G0为(3.44±0.58) mg/L,明显高于术后12个月时的(2.79±0.54) mg/L(P＜0.05).术后1个月时研究组MMF用量为(1.49±0.48) g/d,明显低于对照组的(1.96±0.39) g/d(P＜0.05);术后12个月时MMF用量分别为(1.61±0.77) g/d和(1.68±0.84) g/d(P＞0.05).研究组及对照组急性排斥反应发生率分别为8.7％和9.1％(P＞0.05).研究组MMF相关不良反应总体发生率为47.8％,明显低于对照组的67.3％ (P＜0.05),其中有57.6％的不良反应发生在术后1个月以内.结论 与固定剂量给药方案相比,MPA-C0监测下的MMF个体化治疗最大优势在于可以在不良事件发生前对药量进行主动调整,从而在很大程度上起到了减少MMF相关不良反应的作用,进一步提高了心脏移植疗效.     

肾移植后远期吗替麦考酚酯相关慢性腹泻的药物转换效果观察

目的 探讨肾移植后远期发生吗替麦考酚酯(MMF)相关慢性腹泻时将MMF转换为麦考酚钠肠溶片( EC- MPS)后腹泻的改善情况及对受者机体内环境的影响.方法 26例肾移植受者术后6.2年发生MMF相关的慢性腹泻.确诊后首先将MMF减至最低用量,腹泻仍未减轻,将MMF转换为EC-MPS,360 mg/d.观察转换2周时腹泻的改善状况,若症状无改善,则停用EC-MPS,改用非麦考酚酸类抗排斥反应药物;若症状明显减轻或消失,则第3周时将EC-MPS的用量提高到720 mg/d.提高剂量后再观察2周,若腹泻症状未加重,则维持此剂量,继续观察3个月;若提高剂量后腹泻加重,则重新减量至360 mg/d.药物转换期间观察腹泻症状改善状况以及转换后不同时间的血白细胞计数、血红素、血清丙氨酸转氨酶(ALT)、血肌酐、C-反应蛋白、血钾、血钠、血总二氧化碳(TCO2)及24 h尿蛋白定量等指标.结果 19例于转换药物后2周内腹泻停止,2例腹泻明显减轻,总有效率为80.8％(21/26);另5例转换后腹泻仍较重,停用麦考酚酸类药物;转换药物后,受者的内环境紊乱得到明显改善,血钾、血钠及血TCO2均恢复至正常水平,尤其重要的是,转换前24 h尿蛋白定量为(0.76±0.48)g,转换第3个月为(0.46±0.53)g,明显低于转换前(P＜0.05).结论 移植后晚期发生MMF相关慢性腹泻时将MMF转换为EC-MPS,可使腹泻减轻,并由此改善机体内环境.     

吗替麦考酚酯治疗原发性肾病综合征的前瞻性多中心临床研究

目的观察吗替麦考酚酯(MMF)联合激素治疗原发性肾病综合征(PNS)的疗效及安全性。方法采用前瞻性多中心方法,9个中心共47例患者入选。其中初治患者16例,难治性患者31例。用MMF联合激素治疗。MMF起始剂量为1.0～2.0g/d,至少3个月后开始减量,至12个月时维持在0.75～1.0g/d。口服泼尼松起始剂量0.8～1.0mg·kg-1·d-1,根据疗效减量,至6个月时至少减至传统治疗剂量的50%或以下。定期监测蛋白尿等生化指标及副作用。随访期≥6个月。结果47例患者蛋白尿水平从治疗后第2周起明显下降,由治疗前(6.46±3.18)g/d降至治疗后6个月时的(1.45±2.47)g/d(P<0.01),31/47例达到缓解;治疗后12个月时为(0.96±4.17)g/d(P<0.01),23/26例达到缓解。平均缓解时间为(10.89±11.49)周。初治组与难治性NS组均有效(P<0.01),组间差异无显著性意义(P>0.05)。治疗前后Scr无明显改变(P>0.05),血清白蛋白显著上升(P<0.01),血胆固醇水平明显下降(P<0.05)。微小病变组中6个月时有6/8例已达缓解,治疗后12个月时有4/4例仍处于缓解。系膜增生性肾小球肾炎组中治疗后6个月时有8/10例已达缓解,治疗后12个月时有6/7例仍处于缓解。膜性肾病组中治疗后6个月时有4/10例已达缓解,治疗后12个月时有2/4例仍处于缓解。局灶节段性肾小球硬化组中治疗后6个     

环孢素A与吗替麦考酚酯治疗难治性肾病综合征疗效对比

目的：通过检测临床指标的变化,观察对比环孢素A和吗替麦考酚酯治疗难治性肾病综合征的疗效差异。方法：将本院自2008年1月以来收治的56例原发性难治性肾病综合征患者随机分为CsA、MMF两组,在口服泼尼松0.5mg.kg-1.d-1治疗的基础上,CsA组口服环孢素4mg·kg-1.d-1,MMF组口服吗替麦考酚酯0.75mg2/d,进行1年的随访,在治疗前、治疗3、6、12个月分别记录尿常规、24h尿蛋白定量、肝功能（AST、ALT、Alb）、肾功能（CRE,UA,GLU）、血脂以及环孢素血药浓度等指标的变化,并记录不良反应。结果：从治疗1个月开始,部分患者的尿蛋白定量减轻,血浆白蛋白水平开始有所恢复,前后结果差异有统计学意义（P〈0.05）,两组患者之间差异无统计学意义（P〉0.05）。结论：环孢素A、吗替麦考酚酯均可以有效的治疗难治性肾病综合征,治疗同期两者差异不明显。     

吗替麦考酚酯治疗难治性肾病综合征的临床观察

目的:研究吗替麦考酚酯(MMF)治疗原发性难治性肾病综合征(NS)的疗效及其安全性.方法:对糖皮质激素和环磷酰胺治疗无效或复发的30例原发性难治性肾病综合征患者,采用皮质激素和MMF联合治疗;MMF初始剂量1.0～1.5 g/d,3个月后逐渐减量为半量,疗程6个月以上;同时口服泼尼松20～40 mg/d,根据病情加快皮质激素的撤药速度.定期随访并记录疗效、副作用.结果:MMF 联合皮质激素治疗可以使患者尿蛋白定量下降和血清白蛋白上升(P<0.01),87%患者尿蛋白定量下降, 90%患者血清白蛋白上升,缓解率83%.大部分患者肾功能明显改善至正常,6例透析患者也完全脱离透析.未见明显副作用.结论:MMF对传统免疫抑制剂和糖皮质激素治疗无效或复发的难治性肾病综合征患者有效,未见明显副作用.对MMF的临床应用还有待进一步研究.     

不同霉酚酸剂型在儿童肾移植不同年龄段的暴露差异

目的  探讨儿童肾移植术后服用不同霉酚酸（MPA）制剂在≤12岁与 > 12岁年龄段的暴露差异。方法  回顾性分析73例接受心脏死亡器官捐献（DCD）儿童肾移植受者的临床资料,术后免疫抑制方案均为MPA+他克莫司+糖皮质激素,按照MPA剂型分为A组（37例,服用吗替麦考酚酯胶囊）、B组（28例,服用麦考酚钠肠溶片）和C组（8例,服用吗替麦考酚酯分散片）。并根据移植时患者年龄分为≤12岁年龄段和 > 12岁年龄段。计算不同药物剂型每日给药剂量,采用酶放大免疫法检测MPA血药浓度（C）与曲线下面积（AUC）,比较各组不同时间点和两个年龄段的MPA血药浓度,分析受者术后肾功能恢复情况及并发症发生情况。结果  A、B、C组给药剂量和各时间点血药浓度比较,差异均无统计学意义（均为P > 0.05）。≤12岁年龄段MPA-C_{4 h}、AUC均高于 > 12岁年龄段,差异均有统计学意义（均为P < 0.05）。B组≤12岁年龄段MPA-C_{4 h}高于 > 12岁年龄段,差异有统计学意义（P=0.016）。B组≤12岁年龄段MPA-C_{4 h}较A组和C组高,但差异无统计学意义（P=0.080）。3组急性排斥反应和感染发生率差异均无统计学意义（均为P > 0.05）。结论  不同年龄段儿童肾移植术后服用不同MPA制剂有不同的暴露率,≤12岁儿童肾移植受者暴露率较 > 12岁儿童有升高的趋势,但主要表现在服用麦考酚钠肠溶片的受者中。因此,监测MPA的暴露水平是必要的,对调整不同剂型药物用量具有较大的指导意义。     

吗替麦考酚酯抑制小鼠TH17细胞的分化和增殖

目的 通过观察吗替麦考酚酯(MMF)对小鼠辅助性T淋巴细胞17(TH 17细胞)分化和增殖的影响,探讨MMF的免疫抑制作用及其机制.方法 采用随机数字表法将小鼠分为MMF组与对照组,每组8只.MMF组小鼠每天给予MMF 40 mg·kg-1·d-1灌胃,对照组小鼠每天给予等体积生理盐水灌胃.3周后取小鼠外周血和脾脏,采用流式细胞术检测小鼠外周血和脾细胞中TH17细胞和CD4+CD25+调节性T淋巴细胞(Treg细胞)的比例,并计算出TH 17细胞与Treg细胞的比值;采用酶联免疫吸附试验法分别检测两组小鼠血清中白细胞介素(IL)-17和IL-23的浓度.结果 MMF组外周血和脾细胞中TH17细胞比例分别为(1.95±0.08)％和(2.42±0.06)％,对照组分别为(3.19±0.07)％和(4.21±0.25)％,两组比较,差异均有统计学意义(P＜0.05).MMF组外周血和脾细胞中TH 17细胞与Treg细胞的比值均显著低于对照组(P＜0.05).MMF组小鼠血清IL-17水平明显低于对照组(P＜0.05),而血清IL-23水平高于对照组(P＜0.05).结论 MMF能够明显抑制小鼠体内TH17细胞的分化与增殖,降低TH 17细胞与Treg细胞的比值,减少IL-17的分泌,有利于诱导免疫耐受.     

吗替麦考酚酯联合小剂量泼尼松治疗狼疮性肾炎临床观察

吗替麦考酚酯(MMF)是霉酚酸(MPA)的前体,MPA是单磷酸次黄嘌呤脱氢酶(IMPDH)的可逆、非竞争性抑制剂.IMPDH是鸟嘌呤核苷酸从头合成途径的限速酶.T淋巴细胞和B淋巴细胞比其他类型的细胞更多地依赖这一途径.有研究表明,MMF可以抑制人与大鼠系膜细胞增生,抑制黏附分子的表达[1].我院近期对18例狼疮性肾炎应用吗替麦考酚酯联合小剂量泼尼松治疗,取得了较满意的疗效,现报告如下.     

吗替麦考酚酯在肾内科应用的指导意见

吗替麦考酚酯(MMF,骁悉)是霉酚(MPA)的前体,霉酚酸是嘌呤合成途限速酶-单磷酸次黄嘌呤脱氢酶的可、非竞争性抑制剂。MMF是一种抗代免疫抑制剂,它防治各类实体器官移急性排斥的疗效得到广泛评价。90年后期骁悉逐渐应用于非移植领域,在统性红斑狼疮、肾脏疾病治疗上显示了独特的疗效。骁悉作为免疫抑制剂肾脏内科的应用日益广泛。为了更为理、安全使用MMF,全国部分肾病专(NICC肾科免疫治疗导航顾问团顾)于2002年12月10日在三亚将“骁在肾脏疾病中的应用专家建议书”做第二次修订,经充分讨论,会议达成了下共识。一、适应症1.狼疮肾炎:前…     

Comparison of enteric-coated mycophenolate sodium with mycophenolate mofetil in living renal allograft transplantation

OBJECTIVE: Enteric-coated mycophenolate sodium (MPS) has been developed to decrease the GI side effects of mycophenolate mofetil (MMF). We did a retrospective analysis of 112 patients to compare the safety and efficacy of enteric coated MPS vs MMF in living renal transplantation. METHODS: Patients were divided into two groups. Group A who received MPS [Novartis, Basel, Switzerland] [1.08-1.44 g/d] included 53 patients of mean age 33.5 +/- 11.9 yrs, and M:F gender ratio 37:15 with a mean donor age of 43.2 +/- 9.9 years. Group B who received MMF [1.5-2.0 g/d] included 59 subjects of mean age 33.2 +/- 9.9 yrs and M:F gender ratio 57:6, with a mean donor age of 41.4 +/- 10.9 years. All patients received cyclosporine and prednisolone in addition to mycophenolate. Mean follow-up in the two groups was 11.6 +/- 7.0 and 12.6 +/- 8.5 months, respectively. RESULTS: There were 11 (20.7%) rejection episodes in Group A and 12 (20.3%) rejection episodes in Group B (P = NS). Incidence of CMV disease was 9.61% and 10.1%, and of other infections, 88.7% and 74.7% in Groups A and Group B, respectively [P = NS]. The incidence of GI (18.9% & 20.3%) and hematologic toxicities (9.4% & 5.1%) were similar in the groups. Patient and graft survivals in Group A were 91.9% & 86.6%, and in Group B was 91.3% & 91.3%, respectively [P = NS]. CONCLUSION: Mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with a similar efficacy and safety profile.     

The role of mycophenolate mofetil in clinical renal transplantation

Summary Mycophenolate mofetil (MM) is the ester derivative of mycophenolic acid (MPA), which exerts immunosuppressive activity by inhibiting de novo purine biosynthesis. Following animal models and pilot studies in human renal allograft recipients that confirmed MM's ability to prevent and halt rejection episodes, 3 large multicenter studies of 500 patients each were conducted in North America, Europe, and Australia to compare MM with azathioprine or placebo, all drugs being used in conjunction with prednisone and cyclosporine. The results demonstrated a statistically significant reduction in episodes of allograft rejection in the MM groups with a concomitant reduction in the use of antirejection therapy, especially antilymphocyte antibody therapy. Adverse-event profiles were similar for all groups, although there were slightly more gastrointestinal and tissue-invasive cytomegalovirus (CMV) episodes in the MM groups. It is concluded that MM, which recently received Food and Drug Administration (FDA) approval in the United States, should be an important addition to the transplant physician's immunosuppressive armamentarium.     

The renal benefit of mycophenolate mofetil after liver transplantation

Haywood S, Abecassis M, Levitsky J. The renal benefit of mycophenolate mofetil after liver transplantation.
Clin Transplant 2011: 25: E88–E95. © 2010 John Wiley & Sons A/S. Abstract: Background: The risk and benefit of adding mycophenolate mofetil (MMF) to a standard immunosuppressive regimen at the time of liver transplantation (LT) is not well described. Methods: We performed a retrospective case–control analysis comparing one‐yr outcomes of all LT recipients at our institution treated with post‐operative tacrolimus (TAC), MMF, and steroids vs. TAC and steroids. Results: A total of 101 LT recipients (50:51 case:control) were analyzed. Despite more renal dysfunction at LT, the MMF + TAC group had similar serum creatinine (Cr) and glomerular filtration rate (GFR) as the TAC group one‐yr post‐LT. In this time period, Cr decreased (1.57–1.22 mg/dL, p = 0.04) and GFR increased (57.5–65.1 mL/min per 1.73 m², p = 0.05) in the MMF + TAC group, while Cr increased (1.11–1.35, p < 0.01) and GFR declined (73.5–60.1, p < 0.001) in the TAC group. These findings occurred without a difference in absolute rejection episodes, hospitalizations, infections, deaths, or time to above events (p > 0.05). Subgroup analysis of patients stratified by pre‐transplant renal dysfunction (Cr ≥ 1.2 mg/dL) supported the previous. MMF was reasonably well tolerated with a low rate of discontinuation. Conclusions: The use of adjunctive MMF immediately after LT may protect against calcineurin inhibitor nephrotoxicity, potentially without the need for dose reduction or increased risk of adverse events.     

Efficacy of mycophenolate mofetil on recurrent glomerulonephritis after renal transplantation

Recurrent glomerulonephritis in transplanted kidneys is not rare despite classical immunosuppressive drugs and depends on the etiology of nephropathy. Treatment of recurrence of renal disease on graft remains controversial. We report 6 cases of patients with recurrent glomerulonephritis after renal transplantation treated with mycophenolate mofetil (MMF). The glomerular diseases were Wegener's granulomatosis (n = 1), membranoproliferative glomerulonephritis type I (n = 1), focal and segmental glomerular sclerosis (n = 1), membranous glomerulonephritis (idiopathic membranous nephropathy (n = 1) and systemic lupus erythematous) (n = 1)) and immunoglobulin A nephropathy (n = 1). MMF was introduced because of intolerance of classical immunosuppressive treatment in 2 cases and because of its inefficiency in the other cases. MMF was introduced between 3 months and 36 months (13.5 +/- 7 months) after recurrence of the primitive glomerulonephritis. During combined MMF/cyclosporine/prednisone therapy, only 3 patients responded to MMF. MMF was disrupted precociously in 1 out of 3 patients who stabilized renal function because of discovery of lung cancer and in 2 out of the 3 other patients because of gastrointestinal intolerance and severe anemia. We supposed that MMF could represent a new effective alternative therapy of recurrent glomerulonephritis on renal graft in some cases.     

Effects of mycophenolate mofetil on donor-specific antibody formation in renal transplantation

BACKGROUND: Mycophenolate mofetil (MMF) is a routinely used immunosuppressive agent that selectively blocks T- and B-lymphocyte proliferation. The present study was designed to investigate the effects of this drug on human leukocyte(HLA) antibody production in general and donor-specific antibody (DSA) formation in particular in 154 recipients of renal allografts. PATIENTS AND METHODS: Renal allograft recipients were subdivided into three groups. Group 1 patients (n = 60) had received MMF since transplantation in combination with either cyclosporin A or tacrolimus and steroids. Group 2 patients (n = 29) had received an MMF-free immunosuppressive regimen initially followed by addition of MMF some time later. Group 3 patients (n = 65) had received no MMF. Cyclosporin A or tacrolimus in combination with azathioprine and/or steroids were used for immunosuppression. DSA were demonstrated by enzyme-linked immunosorbent assay (ELISA) for detection of panel-reactive antibodies of HLA class I and II specificity. RESULTS: The HLA antibodies were found in 16.7%, 27.6% and 30.8% of transplant recipients in groups 1, 2 and 3, respectively. DSA were found in 8.3%, 17.2% and 20.0%, and non-DSA in 10.0%, 20.7% and 24.6%, of patients in groups 1, 2 and 3, respectively. CONCLUSION: The MMF reduces anti-HLA class I and II antibody production and consequently DSA production in renal allograft recipients. Our data indicate this effect to be more pronounced in patients given MMF immediately after transplantation than in those in whom MMF is introduced some time later. The presence of DSA in the serum of renal allograft recipients is associated with poorer graft function (higher serum creatinine and more rejection episodes).