HPLC法测定狼疮肾病患者口服吗替麦考酚酯后的血药浓度

目的:建立测定狼疮肾病患者口服吗替麦考酚酯后血药浓度的方法。方法:狼疮肾病患者血样处理后采用高效液相色谱法测定吗替麦考酚酯体内代谢物霉酚酸。色谱柱为SGE Protecol C18,流动相为甲醇-乙腈-0.01%磷酸(23∶37∶40,V/V/V),检测波长为216nm,流速为1.0ml/min,进样量为20μl,柱温为30℃。结果:霉酚酸血药浓度在0.125～10mg/L范围内线性关系良好(r=0.9999);方法回收率为98.67%～104.31%;萃取回收率为83.43%～97.54%,内标(尼美舒利)萃取回收率为79.35%;日内、日间RSD分别为2.6%～7.7%、2.3%～8.5%。结论:本法简单、准确,可用于狼疮肾病患者服用吗替麦考酚酯后霉酚酸的血药浓度检测。     

来氟米特与霉酚酸酯治疗乙肝病毒相关性肾炎的疗效比较

目的比较来氟米特(LEF)与霉酚酸酯(MMF)治疗乙型肝炎病毒相关性肾炎(HBV-GN)的临床疗效。方法 20例血清HBV标记物阳性、病理诊断为乙型肝炎病毒相关性肾炎的患者,随机分为两组,每组10例,第一组采用LEF联合激素治疗,第二组采用MMF联合激素治疗,LEF或MMF正规使用6个月以上。两组中有HBV-DNA复制的均给予干扰素-α或恩替卡韦治疗。观察治疗前及治疗6个月以后的血尿常规、24h尿蛋白定量、肝肾功能、白蛋白及血脂等指标变化,以及用药期间所有不良反应。结果①两组接受治疗后,尿蛋白明显减少(P<0.01),血白蛋白明显上升(P<0.01)。②治疗6个月后LEF组总有效率为80.0%,MMF组总有效率为80.0%,两组之间无统计学差异;其中完全缓解率分别为40.0%和50.0%,部分缓解率分别为40.0%和30.0%,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联合激素治疗均能有效缓解乙型肝炎病毒相关性肾炎,不良反应轻微。     

New immunosuppressive agents in transplantation

Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. Finally, antibody mediated rejection due to donor specific antibodies strongly affects allograft survival.Many drugs have been tested in the last decades, but very few have come to clinical use. The most recent one is CTLA4-Ig (belatacept), a costimulation blockade molecule that targets the second signal of T cell activation and is associated with a better long term kidney function than calcineurin inhibitors, despite an increased risk of acute cellular rejection.The research of new maintenance long-term immunosuppressive agents focuses on costimulation blockade. Agents inhibiting CD40-CD40 ligand interaction may enable a good control of both T cells and B cells responses. Anti-CD28 antibodies may promote regulatory T cells. Agents targeting this costimulation pathways are currently evaluated in clinical trials.Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology.     

恩替卡韦联合霉酚酸酯治疗乙肝病毒相关性肾炎的疗效

目的研究乙肝病毒相关肾炎患者运用恩替卡韦+霉酚酸酯治疗的价值。方法选择我院2015年3月～2018年3月纳入的86例乙肝病毒相关性肾炎患者,按照治疗方式的不同分为两组,各43例,研究组采用恩替卡韦+霉酚酸酯治疗,对照组采用恩替卡韦治疗,对比两组治疗结果。结果研究组总有效率为90.70%,明显高于对照组的79.07%(P0.05);治疗前两组的尿蛋白、血清白蛋白、胆固醇及甘油三酯水平比较,差异无统计学意义(P0.05),治疗后研究组各指标水平均优于对照组(P0.05);治疗前两组食欲、精神、睡眠及日常生活评分比较,差异无统计学意义(P0.05),治疗后研究组各评分均高于对照组(P0.05)。结论恩替卡韦+霉酚酸酯治疗乙肝病毒相关性肾炎效果明显,可有效改善相关指标水平,提高生活质量,促进病情稳定,为预后提供保障。     

吗替麦考酚酯与环磷酰胺联合泼尼松治疗儿童紫癜性肾炎疗效对比

目的:对比分析吗替麦考酚酯与环磷酰胺联合泼尼松治疗儿童紫癜性肾炎的临床疗效及不良反应.方法:将55例紫癜性肾炎患儿随机分为观察组(31例)和对照组(24例),观察组给予吗替麦考酚酯联合泼尼松治疗,对照组给予环磷酰胺联合泼尼松治疗.观察比较两组患儿治疗前后实验室检查指标、完全缓解率及不良反应.结果:两组24h尿蛋白定量、血清白蛋白在治疗后2周均显著改善(P＜0.05),且随着治疗时间的延长,24h尿蛋白逐渐减少,血清白蛋白水平逐渐升高.观察组尿红细胞计数在治疗后1个月显著降低(P＜0.05),对照组尿红细胞计数在治疗后3个月显著降低(P＜0.05).两组总胆固醇、甘油三酯在治疗后6个月显著降低(P＜0.05).观察组完全缓解率90.32％明显高于对照组的63.64％,差异显著(P＜0.05).治疗组不良反应明显低于对照组,但差异无统计学意义(P＞0.05).结论:吗替麦考酚酯联合泼尼松治疗儿童紫癜性肾炎的疗效显著优于环磷酰胺联合泼尼松,且不良反应少,值得临床推广.     

肾移植术后吗替麦考酚酯相关不良反应的危险因素研究

摘 要 目的：探讨肾移植术后吗替麦考酚酯（MMF）所致相关不良反应的危险因素,为规避MMF相关不良反应提供参考。方法：将236例肾移植患者按不良反应类型分为骨髓抑制组、胃肠道反应组、感染组和未发生不良反应的对照组,记录患者的移植时年龄、性别、身高、体重、是否尸肾、体重指数（BMI）、移植时间、透析时间、高血压病史、糖尿病病史、肝病史等一般临床资料,以及服药3,6,12,24,36月时MMF的剂量及谷浓度,肝肾功能、空腹血糖（FPG）、血常规等检查结果,并进行统计学分析。结果：各不良反应组与对照组患者BMI值、用药时间的差异均有统计学意义（P＜0.05）,BMI值越低,用药时间越长,其相应的不良反应发生率越大。骨髓毒性组患者的透析时间明显小于对照组,差异有统计学意义（P＜0.05）,骨髓毒性组患者3,6月时血药谷浓度（C₀）低于对照组,差异有统计学意义（P＜0.05）,用药时间（OR=4.016,95%CI：1.035~10.517,P＜0.05）是MMF骨髓抑制毒性发生的危险因素,术后3月的MMF C₀（OR=1.104,95%CI：1.001~3.218,P＜0.05）是骨髓毒性发生的危险因素。结论：患者服用MMF的用药时间与术后3月时的MMF血药谷浓度是肾移植术后MMF相关不良反应的危险因素,用药时间越长,术后3月时的MMF血药谷浓度越高,发生不良反应的风险越高。     

肾病综合征大鼠模型的建立及酶酚酸酯对其作用的实验研究

目的：研究酶酚酸酯（ＭＭＦ）对大鼠肾病综合征的治疗作用。为临床应用提供依据。方法：经尾静脉一次性注射阿霉素,构建大鼠肾病综合征动物模型。观察ＭＭＦ对大鼠肾病综合征血、尿生化指标、淋巴细胞电压依赖性钾通道及肾脏组织学改变的影响。并与强的松进行对照研究。结果：注射阿霉素１４ｄ。大鼠肾病综合征模型建立。模型鼠表现外周Ｔ淋巴细胞电压依赖性钾通道电流增强。ＭＭＦ治疗可使大鼠尿蛋白和血尿素氮明显下降。血白蛋白上升。肾脏病理显示足突无明显融合。疗效明显优于强的松治疗组。结论：在阿霉素诱导的大鼠肾病综合征模型的形成中,细胞免疫参与了其发病,ＭＭＦ能明显改善模型鼠的肾功能并减轻肾脏组织形态学损害。且疗效优于强的松。     

Use of tacrolimus and mycophenolate mofetil as induction and maintenance in simultaneous pancreas‐kidney transplantation

Abstract Clinical trials using quadruple immunosuppression that include the combination of tacrolimus and mycophenolate mofetil have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas‐kidney (SPK) transplantation. In an attempt to obtain a low rejection rate without antibody induction therapy, we undertook a prospective study of combined tacrolimus and mycophenolate mofetil and steroids as primary immunosuppression for SPK transplantation. In this study, we analyzed 17 patients who received low‐dose intravenous tacrolimus as induction therapy. This was combined with oral tacrolimus, mycophenolate mofetil, and steroids as the primary immunosuppression regimen. There was a significant reduction of empirically and biopsy‐proven rejection with an incidence of 23 % (4 patients). Leukopenia, gastroparesis, and gastrointestinal side‐effects were the cause of discontinuation of mycophenolate mofetil, or low tacrolimus trough level in those patients who developed rejection. All rejection episodes were easy to treat, and none of them required antibody therapy. The combination of tacrolimus with mycophenolate mofetil without antibody induction therapy is effective in preventing early acute rejection. This combination is safe and effective as an alternative immunosuppressive regimen after SPK transplantation.     

霉酚酸酯对大鼠糖尿病肾病及CD2相关蛋白表达的影响

目的研究霉酚酸酯（MMF）对大鼠糖尿病肾病（DN）及CD2相关蛋白（CD2AP）表达的影响。方法纯种雄性SD大鼠24只,分正常对照（A）组、DN模型（B）组和MMF干预DN（C）组。饲养8周后行有关血尿生化指标和光镜组织学、透射电镜、逆转录聚合酶链反应（RT-PCR）CD2AP mRNA表达检测。结果MMF明显减少DN大鼠24h尿蛋白的排泄,预防血肌酐的升高。组织学显示C组大鼠肾小球面积明显减少,系膜增宽及细胞外基质积聚明显改善。电镜下B组大鼠足细胞足突增宽,部分融合,肾小球毛细血管袢基膜增厚,系膜区增宽,系膜基质增多,C组大鼠以上病变都明显减轻。CD2AP mRNA表达在B组显著高于A组和C组。结论MMF具有治疗SD大鼠DN的作用,并且在转录水平逆转肾皮质CD2AP表达上调。