来氟米特与霉酚酸酯治疗表现为肾病综合征的过敏紫癜性肾炎的疗效比较

目的：比较来氟米特（LEF）与霉酚酸酯（MMF）治疗临床表现为肾病综合征的过敏紫癜性肾炎（HSPN）的临床疗效。方法：36例临床表现为肾病综合征的HSPN患者,分别采用激素联合LEF治疗（LEF组,n=18）,或采用激素联合MMF治疗（MMF组,n=18）。LEF或MMF正规使用6个月以上。收集治疗前及治疗6个月以后的血尿常规、尿红细胞计数、24h尿蛋白定量、肝肾功能、白蛋白及血脂等指标,同时记录不良反应。结果：（1）两组接受治疗后,尿蛋白和尿红细胞计数均明显减少（P〈0.01）,血白蛋白明显上升（P〈0.01）。（2）临床缓解率：LEF组总有效率为83.3%,MMF组总有效率为88.8%,两组之间无统计学差异;其中完全缓解率分别为50.0%和44.4%,部分缓解率分别为33.3%和44.4%,均无统计学差异（P〉0.05）。（3）两组患者均耐受良好,无明显副作用。结论：LEF和MMF联合激素治疗表现为肾病综合征的HSPN的临床缓解率相似,不良反应轻微。     

霉酚酸酯对糖尿病大鼠肾脏基质金属蛋白酶9、转化生长因子β1表达的影响

目的 探讨霉酚酸酯（MMF）对糖尿病（DM）大鼠肾脏的保护作用及其机制。 方法 将实验动物分为正常对照组、DM组及MMF治疗组。MMF组给予MMF(15 mg/kg,口服,1次/d) 治疗。8 周后检测各组大鼠尿蛋白量（24 h）、内生肌酐清除率（Ccr）、血糖;HE染色观察肾脏病理改变;免疫组化及RT-PCR法检测肾组织中基质金属蛋白酶9（MMP-9）、转化生长因子β1（TGF-β1）的表达。 结果 DM组大鼠血糖[（22.18±3.36） mmol/L比（6.40±0.87）mmol/L]、尿蛋白量（24 h）[（26.80±0.82） mg比（6.64±1.42） mg]、Ccr[（0.220±0.380） ml/min比（0.098±0.015） ml/min]显著高于对照组（P ＜ 0.05）。MMF组的尿蛋白量（24 h）[（16.17±1.15） mg]、Ccr[（0.220±0.380） ml/min比（0.207±0.377） ml/min]均显著低于DM组（P ＜ 0.05）。与DM组比较,MMF组肾小球肿大、系膜细胞增生显著减轻。肾组织中MMP-9在对照组表达较多,主要在肾小球系膜细胞胞质内及肾小管上皮细胞,DM组表达较弱,MMF组介于两组之间,组间差异均有统计学意义（P < 0.05）。TGF-β1在正常对照组大鼠肾组织有少量表达,在DM组表达较强,在MMF组介于两组之间,组间差异亦均有统计学意义（P < 0.05）。 结论 MMF可降低DM大鼠尿蛋白排泄、Ccr,减轻早期肾小球肥大,此作用可能与MMF上调肾组织中MMP-9表达、下调TGF-β1的表达、减少系膜外基质的沉积有关。     

Remission of resistant MPGN type I with mycophenolate mofetil and steroids

Very few studies have been published on how to treat children with membranoproliferative glomerulonephritis type I (MPGN I), and as yet there is only one report on the use of mycophenolate mofetil (MMF) in children with MPGN I. We report a 12-year-old boy who presented with edema, hypertension, nephrotic range proteinuria, and microscopic hematuria following an upper respiratory tract infection. Laboratory tests revealed a serum creatinine of 90 μmol/l, albumin of 20 g/l, and a C3 of 0.11 g/l (normal range: 0.7–1.4). Renal biopsy showed the presence of MPGN I. Upon failure to induce remission with prednisone, we started the patient on MMF at 500 mg/day (300 mg/m²), increasing up to a final dose of 2 g/day (1200 mg/m²), with a MMF metabolite mycophenolic acid (MPA) target range of 2–5 mg/l. Prednisone was subsequently reduced to alternate day therapy and gradually weaned to 7.5 mg on alternate days over 9 months. Within 4 months of starting MMF therapy, there was significant improvement in serum creatinine (decrease from 156 to 64 μmol/l), serum albumin (increase from 23 to 40 g/l), and proteinuria (decrease from 13 g/day to 40 mg/day). Twelve months following the introduction of MMF into his therapeutic regimen, he remains in remission with no further relapses. In summary, this case suggests that there may be potential benefit for use of MMF in children with refractory MPGN I, which supports the rationale for prospectively evaluating MMF treatment in a treatment trial of refractory MPGN I.     

HPLC法测定注射用吗替麦考酚酯的含量

目的：建立注射用吗替麦考酚酯的含量测定方法。方法：色谱柱为Agilent C8（150×4．6mm,5μm）;流动相为乙腈-水-磷酸缓冲液（取三乙胺10ml,加水990ml,加磷酸调节至pH5．4）（35：45：20）;检测波长为249nm;流速为1．0ml·min^-1;柱温为45℃。结果：吗替麦考酚酯的线性范围为100—1000μg·ml^-1,r=0．9999。平均回收率为101．0％（RSD=1．4％）。结论：方法简便,结果准确,可用于该制剂的含量测定。     

Comparison of high-performance liquid chromatography and enzyme-multiplied immunoassay technique to monitor mycophenolic acid in paediatric renal recipients

Therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) is recommended to guide immunosuppression. High-performance liquid chromatography with ultraviolet (HPLC-UV) or the enzyme-multiplied immunoassay technique (EMIT), used to measure mycophenolic acid (MPA) were compared in an exclusive paediatric renal transplant population. Twenty patients were included as part of the pharmacokinetics study of MMF, and 88 additional samples were drawn for TDM. Agreement between HPLC-UV and EMIT was assessed by the Bland-Altman method. With the two methods, pre-dose concentrations were not normally distributed. After logarithmic transformation, their mean was 0.79 +/- 1.16 mug ml(-1) and their mean difference was 0.34 +/- 0.16 mug ml(-1) [95% confidence interval (95%CI 0.30-0.38 mug ml(-1), with antilogarithmic values of these limits of 1.34-1.46 mug ml(-1)). Area under the curve (AUC)(HPLC) and AUC(EMIT) were normally distributed. Their mean was 52.42 +/- 25.91 mg x h/l and their mean difference was 15.22 +/- 8 mg x h/l (95%CI 11.99-18.45 mg x h/l), the Bland-Altman plot showing a bias proportional to the mean. Our data showed the absence of agreement between the HPLC and EMIT methods, with an average positive bias of 15% with the EMIT. Further studies are required to determine which method is best appropriate for TDM of MMF in children.     

Long-standing refractory polymyositis responding to mycophenolate mofetil: a case report and review of the literature

The authors describe a young patient affected by long-standing polymyositis refractory to conventional treatment who showed a rapid and striking response to mycophenolate mofetil treatment.     

Can mycophenolate mofetil substitute cyclophosphamide treatment of pediatric lupus nephritis?

Intravenous cyclophosphamide (CYC) has been the standard of care to induce remission of severe and active lupus nephritis for more than 20 years. Potential side effects are significant, and failure to achieve remission is still high. Mycophenolate mofetil (MMF) has emerged as a potential alternative to CYC, with an improved safety profile thus far. Results of two mayor randomized controlled trials in adults indicate no evidence of inferiority in patients treated with MMF, less adverse events, and higher rate of complete remission. Experience in the pediatric population is very limited. Thus far, the efficacy, toxicity, and tolerability record of MMF in adults makes it an acceptable alternative to CYC in the induction phase of treatment. Early treatment is desired. Several questions remain: the optimal dose and length of induction with MMF are unknown, the effect of MMF in severe cases of lupus nephritis with renal failure at presentation is unknown, and the compliance with long-term oral treatment in the adolescent population is certainly unknown. In this review, intravenous (IV) CYC induction in the sickest patients (renal failure at presentation) is considered and/or when compliance with oral treatment cannot be established. Also, MMF induction in reliable patients with mostly preserved renal function is considered. Most likely, MMF will serve as a therapeutic bridge between the previously well-known, broad-spectrum immunosuppressive drugs and the new, targeted biological agents.     

己酮可可碱联合霉酚酸酯对高糖诱导人肾小球系膜细胞单核细胞趋化蛋白-1和纤维连接蛋白表达的影响

目的探讨高糖对人肾小球系膜细胞（human mesangial cells,HMCs）单核细胞趋化蛋白-1（monocyte chemoat-tractant protein-1,MCP-1）及细胞外基质的主要成分（extracellular matrix,ECM）纤维连接蛋白（fibronectin,FN）表达的影响及己酮可可碱（pentoxifylline,PTX）联合霉酚酸酯（mycophenolate,MMF）对上述指标的干预作用。方法将培养的HMCs分为8组：正常对照组（NG,5 mmol/L葡萄糖）;高糖组（HG,30 mmol/L葡萄糖）;甘露醇渗透压对照组（Man,5 mmol/L葡萄糖＋25 mmol/L甘露醇）;高糖＋PTX-0.03组（P1,30 mmol/L葡萄糖＋0.03 mg/mL PTX）;高糖＋PTX-0.3组（P2,30 mmol/L葡萄糖＋0.3 mg/mL PTX）;高糖＋MMF-10组（M1,30 mmol/L葡萄糖＋10μg/mLMMF）;高糖＋MMF-100组（M2,30 mmol/L葡萄糖＋100μg/mL MMF）;高糖＋PTX＋MMF组（P＋M,30 mmol/L葡萄糖＋0.3 mg/mL PTX＋100μg/mL MMF）,分别在24、48、72 h采用RT-PCR法和ELISA法检测PTX、MMF及PTX＋MMF对高糖条件下MCs内MCP-1 mRNA及蛋白、FN表达的影响。结果高糖组HMCs MCP-1 mRNA、蛋白的表达及FN的分泌较正常对照组显著增加（P〈0.01）,且48 h表达最高;不同浓度的PTX、MMF均能下调MCP-1 mRNA、蛋白及FN的表达（P〈0.01）;不同浓度的MMF对MCP-1 mRNA、蛋白的表达及FN分泌的抑制程度不同,呈时间剂量依赖性（P〈0.05）;不同浓度的PTX则随着时间的延长对其抑制作用无明显差别;PTX联合MMF组比单独PTX各组在各时间点的抑制程度更明显（P〈0.01）,比单独MMF各组在各时间点抑制作用增强,（24 h,P〈0.05）,但随着时间延长,差异无统计学意义。结论 PTX及MMF可能通过阻抑MCP-1的表达及FN的分泌延缓糖尿病肾病（diabetic nephropathy,DN）中肾小球硬化及间质纤维化的进展,联合给药组作用优于单药,可能从改善血流动力及抗炎角度解释了PTX联合MMF对DN肾脏的协同保护作用。     

Mycophenolate Mofetil Is Effective and Well Tolerated in the Treatment of Refractory Acute and Chronic Graft-versus-Host Disease

We enrolled 11 patients with refractory graft-versus-host disease (GVHD) in a prospective trial evaluating the efficacy of mycophenolate mofetil (MMF). Four (67%) of the 6 patients with acute GVHD and all 5 patients with chronic GVHD responded to MMF.Ten (91%) of the 11 patients were able to decrease steroid use (median decrease, 86%; range, 25%-100%). After a median follow-up of 18 months (range, 1-65 months), 7 patients (64%) remained alive. The adverse events were infectious complications (36%), diarrhea (27%), and neutropenia (18%); the only patient discontinuing MMF did so because of grade 4 neutropenia.This preliminary study suggests that MMF is a well-tolerated agent and has a beneficial effect in the treatment of refractory acute and chronic GVHD.