4种常用免疫抑制剂对器官移植术后口腔临床表现的影响

目的： 通过观察分析肝、肾或造血干细胞移植术后口腔临床表现,探讨移植术后4种常用免疫抑制剂对口腔临床表现的影响。方法： 收集118例接受4种常用免疫抑制剂他克莫司、西罗莫司、环孢素或吗替麦考酚酯的实体器官或造血干细胞移植术后患者,采用问卷调查、口腔临床检查,记录患者术后口腔临床表现和免疫抑制剂的使用情况,并采用SPSS 21.0软件包对数据进行统计学分析。结果： 术后使用他克莫司的患者,口腔苔藓样病变和唇炎的发生率均显著低于未使用他克莫司组（P<0.01）;术后使用环孢素的患者,口腔苔藓样病变的发生率显著高于未使用环孢素组（P<0.05）,且唇炎的发生率显著高于未使用环孢素组（P<0.01）;术后使用他克莫司的患者,苔藓样病变、唇炎的发生率均显著低于使用环孢素组（P<0.01);术后使用吗替麦考酚酯的患者,自觉口干的发生率显著低于未使用吗替麦考酚酯组（P<0.01）;术后使用西罗莫司的患者,口腔临床表现发生率无明显降低。结论： 移植术后使用他克莫司,可改善口腔苔藓样病变和唇炎的症状,效果优于环孢素。使用吗替麦考酚酯可改善患者自觉口干症状。     

肾小球系膜区微量IgM沉积在儿童微小病变型肾病综合征中的意义

目的 探讨肾小球系膜区微量IgM 沉积在儿童微小病变型原发性肾病综合征(PNS)中的意义。方法 以临床诊断为PNS、病理诊断为微小病变(MCD)及肾组织微量IgM 沉积的106 例患儿为研究组,无免疫复合物沉积的MCD 型PNS 患儿81 例为对照组,回顾性分析两组患儿的临床特点、微量IgM 沉积对糖皮质激素及免疫抑制剂疗效的影响。患儿均口服足量泼尼松治疗,对糖皮质激素耐药者或频复发者联用免疫抑制剂治疗。结果 研究组糖皮质激素耐药率高于对照组(27.2% vs 12.3%,PPP>0.05)。研究组和对照组频复发病例联用MMF 治疗后复发频率均显著减少(P结论 MCD 型PNS 患儿肾脏的微量IgM 沉积可能是糖皮质激素耐药及频复发的重要因素;糖皮质激素耐药及频复发患儿联用MMF 治疗可能是较好的治疗方案。     

Comparative Analysis of Calcineurin Inhibitor–Based Methotrexate and Mycophenolate Mofetil–Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P < .001) and grade III to IV acute GVHD (RR, 1.93; P = .006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P = .008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.     

吗替麦考酚酯联合泼尼松治疗儿童肾病综合征的效果分析

目的 探究吗替麦考酚酯分散片联合醋酸泼尼松片治疗儿童肾病综合征的效果。方法 选择2016年1月—2018年1月于常州市儿童医院接受治疗的50例肾病综合征患儿作为研究对象,采用奇偶数法将患儿均分为两组,每组各25例。对照组接受环孢素软胶囊联合醋酸泼尼松片治疗,实验组接受替麦考酚酯分散片联合醋酸泼尼松片治疗,两组均持续治疗6个月。对比两组临床治疗总有效率、治疗中不良反应发生率及治疗前后IgA、IgG、IgM、蛋白排泄率（UAER）、血浆白蛋白（Alb）、尿素氮（BUN）、血肌酐（Scr）等指标变化。结果 治疗后,实验组治疗总有效率显著高于对照组（P<0.05）。治疗后,两组IgA、IgG、IgM水平均高于治疗前,且实验组高于对照组（P<0.05）,但对照组治疗后IgM水平与治疗前差异无统计学意义（P>0.05）。治疗后,两组UAER、BUN及Scr水平均显著降低,而Alb显著升高,且实验组改善更显著（P<0.05）。两组治疗期间药物不良反应发生率无显著差异（P>0.05）。结论 吗替麦考酚酯分散片联合醋酸泼尼松片治疗儿童肾病综合征的效果良好,能够显著改善患儿免疫功能和肾功能,提高临床疗效,且治疗安全性较高。     

Therapeutic drug monitoring of mycophenolate in adult solid organ transplant patients: an update

Introduction: Mycophenolate (MPA) therapeutic drug monitoring (TDM) in adult solid organ transplant recipients was summarized extensively in consensus reports published between 2009 and 2011. Thus, this review provides an update on the science of MPA TDM over the past 5 years.

Areas covered: PubMed and Google Scholar (January 2010-January 2016) were searched; relevant articles from bibliographies of identified articles were extracted for further review. New evidence on TDM-guided dosing in MPA efficacy and toxicity and best approaches for estimating MPA area-under-the-curve for TDM were retrieved.

Expert opinion: Since 2011, little advancement in consensus on MPA TDM has been established for any type of solid organ transplant. Lack of systematic studies validating or further defining MPA’s target range suggests that routine TDM is still unwarranted.

Accurate, precise, and user-friendly limited sampling strategies (LSSs) are available in specific patient populations taking mycophenolate mofetil but not enteric-coated mycophenolate sodium. In absence of outcome data, routine use of LSSs in MPA TDM still cannot be recommended.

Further research should attempt to define factors that modulate MPA’s pharmacokinetics to elucidate their impact on utility of TDM. Future studies should also validate LSSs in larger patient populations and demonstrate benefits of LSSs in improving patient outcomes.     

霉酚酸酯及血管紧张素Ⅱ对人近端肾小管上皮细胞增殖的影响

目的:研究霉酚酸酯(MMF)及血管紧张素Ⅱ(AngⅡ)对人肾小管上皮细胞(HK-2)增殖的影响。方法:将培养的HK-2分别用MMF及AngⅡ刺激并采用MTT法检测HK-2增殖的情况。结果:与空白对照组比较,MMF使HK-2的增殖降低(P<0·05);AngⅡ使HK-2的增殖明显增加(P<0·01);先加入MMF后再用AngⅡ刺激HK-2,HK-2增殖低于AngⅡ单用组(P<0·01)。结论:MMF能够抑制HK-2增殖及抑制AngⅡ引起的人肾小管上皮细胞的增殖。     

两种药物治疗新月体性狼疮性肾炎的疗效比较

目的 比较霉酚酸酯(MMF)与环磷酰胺(CTX)治疗新月体性狼疮性肾炎(CLN)的疗效.方法 对MMF组(治疗组)10例和CTX组(对照组)10例进行一般状况、临床表现、病理特征、治疗缓解率、复发率、不良反应发生率及预后的回顾性对比分析.结果 两组患者一般状况、临床表现及狼疮活动性指数(SLE-DAI)、病理损害程度间差异无统计学意义,治疗组和对照组治疗12个月时缓解率分别为70%和60%,治疗组完全缓解率(50%)显著高于对照组(30%),复发率(10%)则显著低于对照组(40%).对照组2例(20%)死亡;治疗组无死亡病例.结论 与环磷酰胺方案比较,霉酚酸酯组取得更高的完全缓解率和低复发率,且感染不良反应较少见,安全性好.     

霉酚酸酯联合强的松治疗难治性狼疮性肾炎的疗效

目的：研究霉酚酸酯与强的松联合应用治疗难治性狼疮性肾炎的临床疗效性。方法：将2013年6月～2014年5月我院收治的156例难治性狼疮性肾炎患者随机分为两组,对照组给予环磷酰胺冲击疗法联合强的松治疗,实验组给予霉酚酸酯联合强的松治疗,观察并比较两组治疗前后的肝肾功能、临床疗效和不良反应。结果：两组患者治疗前的肝、肾功能无显著差异（P>0.05）,治疗后实验组肾功能改善情况及临床疗效均明显优于对照组,且肾功能损害程度及不良反应比对照组轻（P<0.05）。结论：霉酚酸酯与强的松联合应用治疗难治性狼疮性肾炎,具有较好的临床疗效和较轻的不良反应,值得临床推广。     

Comparison of the immunogenicity of Dukoral® oral cholera vaccine between renal transplant recipients on either a calcineurin inhibitor or mycophenolate – A controlled trial

BackgroundThe evidence for recommendations regarding vaccination in solid organ transplant recipients is sparse. There is little data comparing vaccine responses between groups on different immunosuppressive drugs. This study was conducted to evaluate the antibody response to Dukoral® oral cholera vaccine in renal transplant recipients (RTR).MethodsIn a single-center non-randomized controlled clinical trial, healthy volunteers (n = 21) and renal transplant recipients (n = 30) were vaccinated with the oral whole cell/recombinant B subunit cholera vaccine Dukoral® (Valneva Inc., Vienna, Austria). The RTR were stratified according to their maintenance immunosuppressive therapy: either prednisone and a calcineurin inhibitor (cyclosporine A or tacrolimus; P/CNI group; n = 15) or prednisone and mycophenolate (P/MMF group; n = 15). All volunteers ingested Dukoral® at baseline and at day 14. Serum samples were drawn at day 0 and day 21. The primary outcome was seroconversion, defined as either a 3-fold IgA serum titer increase in anti-cholera toxin B antibodies and/or a 4-fold rise in the serum vibriocidal titer.ResultsFollow-up was complete. Seroconversion after vaccination was 57% (standard error, SE 9%) in RTR and 81% (SE 9%) in healthy controls (Relative Risk, RR 0.70; 95% CI 0.48–1.02). When stratified according to maintenance immunosuppression, the seroconversion rate was 67% (SE 12%) in the P/CNI group (RR compared with controls 0.82; 95% CI 0.55–1.25) and 47% (SE 13%) in the P/MMF group (RR compared with controls 0.58; 95% CI 0.32–1.03).ConclusionAdverse events were mild to moderate and transient. The response to Dukoral was weaker and the seroconversion rate was lower in renal transplant recipients than in healthy controls. In particular, those using mycophenolate had a poor response. Nevertheless, more than half of the transplant recipients seroconverted. Therefore oral vaccines should not be discarded as a potential tool for protection of solid organ transplant recipients.This trial is registered in clinicaltrials.gov under NCT01109914.