临床肾移植若干重要问题探讨

发布时间：2018-05-08 18:49

本文选题：肾移植 + 聚乙二醇干扰素α-2b　；参考：《华中科技大学》2014年博士论文

【摘要】：目的探讨聚乙二醇干扰素a-2b联合利巴韦林治疗肾移植术后丙型肝炎的疗效及安全性。方法对9例肾移植术后1年以上、血肌酐稳定在正常范围的丙型肝炎患者,采用聚乙二醇干扰素α-2b(佩乐能)50μg皮下注射,每周1次；同时口服利巴韦林400-600mg/d治疗。每月检测HCV-RNA, HCV-RNA转阴后继续巩固治疗3-9月。观测病毒学应答情况,同时观察肝肾功能、血常规变化以及治疗过程中出现的不良反应。结果9例患者的总疗程为4-20月,其中6例(66.7%)获得满意的持续病毒学应答(SVR),观查至停止干扰素治疗后6月未出现复发；2例在获得快速病毒学应答后,于巩固治疗3月停止治疗后复发；1例在治疗8个月的过程中未见明显病毒学应答。治疗中所有患者血肌酐均在正常范围内波动,未见急性排斥反应迹象。治疗过程中的主要不良反应包括流感样症候群(发热、肌肉酸痛、食欲不振等)、一过性骨髓抑制以及贫血等。所有不良反应未经处理或经对症处理后均可缓解或耐受。结论聚乙二醇干扰素α-2b联合利巴韦林治疗移植肾功能稳定的丙型肝炎患者有确切疗效,对移植肾功能无明显影响,无严重不良反应,较为安全。目的探讨肾移植术后间质性肺炎的临床病程规律、治疗原则及影响转归的主要因素。方法回顾性分析2006年11月至2013年12月诊治的30例同种异体肾移植术后早期间质性肺炎患者的临床资料,对其临床表现、病程进展规律、治疗措施及临床转归进行分析。结果30例患者中29例于肾移植术后2-6月内发病,其病程进展具有较一致的规律性,整个病程时间平均34.9±7.5天,通过每周肺部CT检查,发现起病到病程高峰平均14.8±1.9天,病程达到高峰后一般维持7.3±3.6天,即会出现明显的病程好转。若病程高峰时的肺部CT表现严重,且维持时间长而未出现病程好转,则往往预后较差。病程恢复期平均13.1±3.7天。治疗上通过对激素、抗生素、抗真菌药物的使用进行优化调整,结合营养支持、提高免疫力以及大幅减量或停用免疫抑制剂等措施,病程高峰期胸部CT表现程度为较轻及中度的23例患者均治愈出院,胸部CT表现较重的7例患者中3例治愈,4例死亡。结论肾移植术后早期间质性肺炎具有比较规律的病程进展特点。对目前的大多数文献报道的治疗方案,包括甲基强的松龙的使用、抗生素的使用、抗真菌药物的使用、营养支持和免疫抑制剂的使用等方面进行进一步的优化调整,在避免过度医疗的情况下取得了良好的治疗效果。目的探讨和比较相同浓度下即复宁和ATG-F杀伤淋巴细胞的效价。方法将相同浓度的即复宁和ATG-F倍比稀释,对正常受试者外周血淋巴细胞进行淋巴细胞毒试验(CDC),用流式细胞仪进行相关检测。结果1.体外淋巴毒试验中即复宁和ATG-F对6名健康志愿者外周血淋巴细胞的杀伤作用随着稀释滴度的增加逐渐下降。即复宁滴度为1：1时杀伤淋巴细胞比率最高,54.06%-82.49%(66.24±10.35),在1：128时杀伤比率10%(5.59±2.59)。ATG-F滴度为1：1时杀伤效果最强,38.06%-70.38%(59.8±11.8),在1：64时杀伤比率10%(6.31±4.80)。2.即复宁对外周血T淋巴细胞杀伤比率平均为51.23%,ATG-F为49.84%。即复宁对B淋巴细胞杀伤比率平均为30.45%,ATG-F则为24.31%(P=0.0002)。结论即复宁和ATG-F均可显著清除正常人外周血淋巴细胞。相同浓度下,即复宁的效价大约是ATG-F的2倍。此外,即复宁比ATG-F有更强的清除B细胞的作用。目的探讨肾移植受者长期服用五酯胶囊提高他克莫司(Tac)血药浓度的安全性和适应症。方法在Tac谷浓度相当的移植肾功能稳定受者中根据是否长期服用五酯胶囊分为五酯组10例和对照组10例,比较两组间的Tac药代学参数,并比较五酯胶囊对不同CYP3A5基因型受者服用Tac剂量的影响。结果五酯组服用五酯胶囊平均31月,Tac平均谷浓度6.3μg/L；对照组Tac平均谷浓度5.9μg/L。五酯组Tac的平均峰浓度和曲线下面积均略高于对照组,达峰时间稍延迟,但总体差异无统计学意义。CYP3A5*1/*3型在二组都占60%,而五酯组受者的平均Tac剂量比对照组下降约36%(p0.01)。*1/*1型受者在五酯组占30%,其服用五酯胶囊后Tac的平均剂量比*1/*3型受者减少更明显,几乎达到平均服药量最低的对照组*3/*3型受者的Tac服药量。结论肾移植后长期服用五酯胶囊提升Tac浓度的方法对大部分CYP3A5*1基因型受者安全有效,尤其对CYP3A5*1/*1型受者。
[Abstract]:Objective to evaluate the efficacy and safety of peginterferon a-2b combined with Leigh Bhave Lin in the treatment of hepatitis C after renal transplantation.
Methods 1 years after renal transplantation, 9 patients with normal blood creatinine in the normal range of hepatitis C were subcutaneously injected with peginterferon alpha -2b (Pepe -2b), 1 times a week, and 1 times a week. At the same time, Leigh Bhave Lin 400-600mg/d was taken orally. HCV-RNA was detected each month and HCV-RNA was further consolidated after 3-9 months. The response of Virology was observed. At the same time, liver and kidney function, blood routine changes and adverse reactions during treatment were observed.
Results the total course of treatment for 9 patients was 4-20 months, of which 6 cases (66.7%) received a satisfactory sustained virological response (SVR), and no recurrence occurred in June after the observation of cessation of interferon therapy. After the rapid virology response was obtained, the relapse after the consolidation therapy was stopped in March, and the 1 cases had no obvious virological response during the treatment of 8 months. Blood creatinine in all patients fluctuated in the normal range, and no signs of acute rejection were found. The major adverse reactions during the treatment included influenza like syndrome (fever, muscle soreness, loss of appetite, etc.), an excessive myelosuppression and anemia. All adverse reactions were relieved or tolerated after untreated or symptomatic treatment.
Conclusion peginterferon alpha -2b combined with Leigh Bhave Lin is effective in the treatment of hepatitis C patients with stable renal function, and has no obvious effect on renal transplantation, no serious adverse reaction and safe.
Objective to investigate the clinical course, principles and main factors affecting the prognosis of interstitial pneumonia after renal transplantation.
Methods the clinical data of 30 patients with early interstitial pneumonia after the allograft kidney transplantation were analyzed retrospectively. The clinical manifestations, the progress of the course of the disease, the treatment measures and the clinical outcome were analyzed.
Results of the 30 patients, 29 were found within 2-6 months after renal transplantation. The course of the disease progresses with a consistent regularity. The average duration of the disease was 34.9 + 7.5 days. Through the weekly lung CT examination, the average duration of the onset was 14.8 + 1.9 days, and the duration of the disease was generally 7.3 + 3.6 days after the course reached the peak. When Cheng Gaofeng had a severe CT performance in the lungs and maintained a long duration without a improvement in the course of the disease, the prognosis was poor. The average duration of the course was 13.1 + 3.7 days. The treatment of hormone, antibiotics and antifungal drugs was optimized, combined with nutritional support, improvement of immunity, significant reduction or stop use of immunosuppressants. At the peak of the disease, 23 cases of mild and moderate CT were cured and discharged. 3 of the 7 patients with severe chest CT were cured and 4 died.
Conclusion early interstitial pneumonia after renal transplantation has a relatively regular course of progression. Most of the present treatment schemes, including the use of methylprednisolone, the use of antibiotics, the use of antifungal drugs, nutritional support and the use of immunosuppressive agents, are further optimized and avoided. Under the condition of excessive medical treatment, good therapeutic effect has been achieved.
Objective to investigate and compare the titers of the killing lymphocytes of Fu Ning and ATG-F at the same concentration.
Methods the lymphocyte toxicity test (CDC) was carried out on peripheral blood lymphocytes of normal subjects, and the flow cytometry was used to detect the same concentration of the peripheral blood lymphocytes of the normal subjects.
Results 1. in the 1. in vitro lymphatic test, the killing effect of tannin and ATG-F on the peripheral blood lymphocytes of 6 healthy volunteers gradually decreased with the increase of the dilution titer. That is, the ratio of the killer lymphocyte was the highest when the tannin titer was 1:1, 54.06%-82.49% (66.24 + 10.35), and the killing ratio of 10% (5.59 + 2.59).ATG-F titer at 1:1 at 1:1. The injury effect was the strongest, 38.06%-70.38% (59.8 + 11.8), the killing ratio at 1:64 was 10% (6.31 + 4.80).2., that was, the average killing ratio of T lymphocyte in the peripheral blood of the Ningxia was 51.23%, ATG-F was 49.84%., the average of B lymphocyte killing ratio was 30.45%, and ATG-F was 24.31% (P= 0.0002).
It is concluded that tannin and ATG-F can clear the peripheral blood lymphocytes of normal people. Under the same concentration, the titer of tannin is about 2 times that of ATG-F. In addition, the effect of tannin is stronger than that of ATG-F.
Objective to investigate the safety and indications of long-term use of five ester capsules in improving the plasma concentration of tacrolimus (Tac) in renal transplant recipients.
Methods the Tac pharmacokinetic parameters between the two groups were compared and the effects of the five ester capsules on the dose of Tac were compared between the two groups according to whether the five ester capsules were divided into five esters in 10 cases and the control group were divided into 10 cases and the control group.
Results the average concentration of Tac in the five ester group was 31 months and the average Valley concentration was 6.3 g/L, and the average peak concentration of Tac in the control group was slightly higher than that of the control group, and the area under the curve was slightly higher than that of the control group. The peak time was slightly delayed, but the overall difference was not statistically significant in the two groups of the two groups and 60%, while the average Tac of the five ester group was Tac. The dosage of the dose compared to the control group was about 36% (P0.01) and the group.*1/*1 was 30% in the five ester group. The average dose of Tac after taking five ester capsules was more obvious than that of the *1/*3 type, and it almost reached the Tac dosage of the *3/*3 type recipient in the control group with the lowest average dosage.
Conclusion long term use of five ester capsules to enhance Tac concentration after renal transplantation is safe and effective for most CYP3A5*1 genotype recipients, especially for CYP3A5*1/*1 type recipients.

【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R699.2

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