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。     

霉酚酸酯对糖尿病大鼠肾小管上皮细胞转分化的影响

目的探讨霉酚酸酯(MMF)对糖尿病大鼠肾小管上皮细胞转分化的影响及其可能机制。方法雄性SD大鼠28只,随机选取8只作为正常对照组(N组),其余20只注射链脲佐菌素(STZ)制作糖尿病模型,并随机分为糖尿病组(DM组)、霉酚酸酯组(M组)。12周后测量大鼠血糖、体质量、肾质量/体质量、24 h尿蛋白定量、血肌酐(SCr),观察肾小管间质病理形态学变化,应用免疫组化技术和Western blot检测肾组织中α-平滑肌肌动蛋白(α-SMA)及转化生长因子β1(TGF-β1)的表达。结果 DM组血糖、肾质量/体质量、24 h尿蛋白定量、血SCr、肾小管-间质损伤指数(TII)均明显高于N组(P<0.01),M组除血糖、体质量外(P>0.05),其余指标均明显低于DM组(P<0.01);免疫组化结果显示,DM组肾小管上皮细胞胞浆中α-SMA、TGF-β1表达均明显高于N组(P<0.01),M组明显低于DM组(P<0.01);Western blot结果显示,DM组肾组织α-SMA、TGF-β1表达较N组分别增加3.4倍与1.1倍,M组肾组织α-SMA、TGF-β1表达较DM组分别下降55%与40%。结论 MMF能下调糖尿病大鼠肾小管上皮细胞α-SMA、TGF-β1的表达,抑制肾小管上皮细胞转分化,起到肾脏保护作用。     

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.     

肝移植受者早期霉酚酸药代动力学临床特点

目的:探讨联合应用他克莫司(FK506)治疗肝移植受者早期霉酚酸(MPA)药代动力学的临床特点。方法:71例肝移植受者术后联合应用FK506和霉酚酸酯(MMF)治疗,MMF单剂口服剂量为1.0g,每日2次。患者术后1至2周内,分别在服药前及服药后0.5、1、1.5、2、4、6、8、10和12h取外周血,采用高效液相色谱法(HPLC)测定其血浆MPA浓度,分别标为MPA-C0～12h,并计算其曲线下面积(AUC)。同一天测定FK506谷浓度(FK506-C0h)及肝、肾功能和血细胞计数。结果:合并108套数据,MPA-AUC0～12h平均为(45.77±18.69)μg·h/ml(范围:10.66～117.01μg·h/ml)。MPA-C0～12h与MPA-AUC0～12h均相关(P0.05)。血清白蛋白(ALB)异常者的MPA-AUC0～12h均显著低于ALB正常者(P<0.05)。结论:原位肝移植后患者个体间早期MPA-AUC0～12h差异很大;单个时间点MPA浓度不能有效反映其全程的血药浓度。FK506-C0h不影响MPA-AUC0～12h,而血清ALB浓度则对其有显著影响。     

霉酚酸酯对弥漫增生型狼疮性肾炎患者的疗效观察

目的 :比较霉酚酸酯 (MMF)和环磷酰胺 (CTX)冲击疗法治疗Ⅳ型狼疮性肾炎的疗效及不良反应。方法 :A组 2 0例 ,间断性CTX冲击疗法联合激素 1mg·kg-1·d-1治疗 ;B组 2 0例 ,MMF联合激素治疗。随访 12个月。结果 :CTX组、MMF组治疗LN均能降低蛋白尿、血尿 ,改善肾功能和免疫指标 ,两组无统计学意义 (P >0 .0 5 ) ,但MMF组治疗效果优于CTX组。不良反应 ,MMF组明显低于CTX组 (P <0 .0 5 )。结论 :CTX、MMF都能有效地控制狼疮性肾炎 ,且MMF具有一定的优越性     

狼疮性肾炎患者应用环磷酰胺联合霉酚酸酯治疗的临床疗效

目的 探究狼疮性肾炎患者应用环磷酰胺联合霉酚酸酯治疗的临床效果。方法 选取2016年5月至2019年6月本院收治的62例狼疮性肾炎患者,随机分为观察组与对照组,各31例。观察组给予泼尼松+环磷酰胺+霉酚酸酯治疗,对照组给予泼尼松+环磷酰胺治疗,比较两组临床疗效及治疗前后免疫指标[免疫球蛋白A(IgA)、免疫球蛋白G(IgG)及免疫球蛋白M(IgM)]、肾功能指标[24 h尿蛋白定量,血肌酐]、血清C反应蛋白（CRP）、血清胱抑素C(CysC)、血清转化生长因子-β1(TGF-β1)水平及用药安全性。结果 观察组治疗总有效率为96.77%,显著高于对照组的80.65%(P<0.05)。治疗后,观察组IgA、IgG、IgM、24 h尿蛋白定量、血肌酐、CRP、CysC及TGF-β1水平均显著优于对照组（P<0.05）。两组胃肠道不适发生率比较差异无统计学意义,观察组感染及肝功能异常发生率显著低于对照组（P<0.05）。结论 狼疮性肾炎患者应用环磷酰胺联合霉酚酸酯治疗效果显著,能有效改善免疫功能、肾功能及炎症反应,且安全性较高。     

Efficiency of Rituximab in treating children with refractory nephrotic syndrome北大核心CSCD

目的评价利妥昔单抗(RTX)在难治性肾病综合征患儿中维持缓解的有效性。方法回顾性研究。将2018年11月至2020年11月华中科技大学同济医学院附属武汉儿童医院肾内科诊断为难治性肾病综合征的22例患儿纳入研究, 予RTX治疗。外周血中CD19+B淋巴细胞≥1%总淋巴细胞者追加1剂RTX(375 mg/m2), 每例患儿使用3~4剂, 早期停用钙调神经磷酸酶抑制剂(CNI), 后续使用霉酚酸酯治疗。采用Kaplan-Meier法对RTX治疗后患儿的蛋白尿无复发率和无频复发肾病综合征或激素依赖肾病综合征发生率进行分析, 采用Wilcoxon秩和检验对使用RTX前后的复发次数进行分析。采用秩和检验对RTX治疗前后患儿的体质量指数(BMI)及身高进行比较。结果 22例患儿中, 20例患儿完成治疗方案, 1年和2年的蛋白尿无复发生存率分别为85%和40%, CNI停用后复发频率降低。所有患儿BMI及身高在使用RTX治疗前与使用RTX 1年后、2年后比较, 差异均有统计学意义(均P<0.05), 使用RTX后1、2年比较, 差异均无统计学意义(均P>0.05)。结论使用RTX在停用激素和其他免疫抑制剂情况下也可有效降低难治性肾病综合征的复发率, 同时可使患儿BMI及身高得到明显改善。RTX治疗难治性肾病综合征患儿安全有效。     

Idiopathic granulomatous mastitis in seventy seven-female patients: Management,follow up of an overlooked immune-mediated disease,and review of literature

BackgroundIdiopathic granulomatous mastitis (IGM) cases have been increasingly recognized in the context of autoimmune diseases. Hence rheumatologists need to be acquainted with IGM detection and management. Although studies evaluating the response to the emerging immunosuppressive drugs were promising, prospective studies still remain scarce.Aim of the workThis prospective study aimed to evaluate previous immunosuppressive regimens in the management of IGM cases.Patients and methodsSeventy seven female IGM patients were followed up, and stratified into 2 groups based on the treatment modalities received: double therapy (Group D, n = 17) who received steroids and methotrexate (MTX), and triple therapy (Group T, n = 60) who received steroids, MTX and mycophenolate mofetil (MMF). Each group was followed up monthly till the end of treatment then every 3 months after stopping treatment for at least 2 years, and the patients' data were recorded on 3 visits (V1, V2, and V3).ResultsFemale patients mean age was 33.9±6.2 years. IGM lesions improved in the form of pain relief, resolution of lumps; replacement of inflammatory lesions by granulation tissue, with superiority of triple therapy group T over double therapy in group D regarding significantly shorter duration of treatment (26.5±3.1 vs 18.1±4.4 months)(p < 0.001), and decreased time needed to steroid tapering (14.1±3.6 vs 5.5±5.2 months)(p < 0.001). No recurrence was noticed.ConclusionsTreatment of IGM has been successful using MTX, or MTX and MMF besides to steroid therapy. Triple therapy was significantly superior with shorter duration of treatment and faster feasibility of steroid tapering.