【作者】 徐萍；

【导师】 郑红光；

【作者基本信息】 大连医科大学 ， 内科学， 2015， 硕士

【摘要】 目的:本研究采用单中心、前瞻性、随机对照的研究方法,观察他克莫司联合糖皮质激素治疗特发性膜性肾病的长期有效性及安全性,探索他克莫司在治疗特发性膜性肾病患者中的血药谷浓度的变化及其与疗效和安全性之间的关系。为临床治疗特发性膜性肾病提供更好的循证医学依据。方法:入选2011年1月-2013年2月于沈阳军区总医院肾内科行肾活检穿刺术后,病理诊断为特发性膜性肾病的患者共81例,其中男性45例,女性36例,年龄波动在18-70岁之间,平均年龄(43.13岁)。随机分为两组,TAC组(41例):采用他克莫司联合糖皮质激素进行治疗,TAC起始剂量为0.05mg-0.1mg/(Kg·d),12小时1次,定期进行血药谷浓度的监测,逐渐进行药物减量,疗程不小于24个月。CTX组(40例):采用CTX静脉冲击治疗方法,CTX累积总剂量波动在0.15-0.2g/kg,每月分两次隔日静滴,每次0.6g,连续使用6个月,此后,则调整为每3个月冲击治疗1次。两组患者均联合口服糖皮质激素(泼尼松片),起始剂量0.75mg/(kg.d),逐渐进行规律减量。对患者进行为期24个月的随访,定期监测患者的24小时尿蛋白定量、尿常规以及相关的重要生化指标。记录患者的临床缓解时间及复发等情况。结果:经过24个月的治疗,两组患者24小时尿蛋白定量、血清白蛋白、血清总蛋白较治疗前明显好转(p<0.01)。TAC组经过治疗6个月和18个月的总缓解率明显高于CTX组的总缓解率(p<0.05)。两组患者经过12个月和24个月的治疗后,总缓解率无明显统计学差异(p>0.05)。经过治疗24个月TAC组的完全缓解率明显高于CTX组的完全缓解率(p<0.05)。CTX组经过治疗18个月后的复发率明显高于TAC组治疗18个月后的复发率(p<0.05)。TAC组经过治疗6个月、12个月、18个月及24个月的平均血药谷浓度分别为5.65ng/ml、4.86ng/ml、2.83ng/ml和2.71ng/ml,其有效血药谷浓度范围波动在3.1~8.5ng/ml、3.1~7.6ng/ml、1.4~4.56ng/ml、1.4~4.35ng/ml。治疗6个月及12个月TAC血药谷浓度与治疗效果成正相关(p<0.05),治疗18个月及24个月TAC血药谷浓度与治疗效果无相关性(p>0.05)。TAC组糖耐量异常发生率明显高于CTX组糖耐量发生率(P<0.05)。结论:治疗24个月后,他克莫司组的临床完全缓解率明显高于环磷酰胺组。.应用他克莫司联合糖皮质激素治疗特发性膜性肾病在短期诱导特发性膜性肾病的缓解和长期治疗特发性膜性肾病的完全缓解情况较环磷酰胺组均具有较好的优越性。长期低血药浓度维持治疗特发性膜性肾病复发率明显低于环磷酰胺组。他克莫司组的主要不良反应为糖耐量异常,并且他克莫司组糖耐量异常发生率较环磷酰胺组高。环磷酰胺组的不良反应主要为肝功能异常。更多还原

【Abstract】 Objective:To evaluate the long-term efficacy and safety of using the tacrolimus(TAC) combined with corticosteroids in treatment of idiopathic membranous nephropathy patients. To study the relationship between the plasma concentration of tacrolimus and the efficacy and the safety.Aimed to provide the better basis of evidence-based medicine for the clinical treatment of IMN patients.Methods: Eighty-one patients with biopsy-proved IMN and nephrotic syndrom were randomly divided into two groups from January 2011 to February 2013 in the General Hospital of Shenyang Military Region,the nephrology department.Among the81 patients,45 were male,36 were female.The age between 18 years old and 70 years old,the mean age was 43.13 years old.Randomly divided into two groups,TAC group(41):using tacrolimus plus corticosteroids to treat the IMN patients,tarcrolimus was given at 0.05-0.1mg/(kg·d) initially,once 12 hours,then monitoring the plasma concentration of tacrolimus.CTX group(40):using CTX plus corticosteroids to treat the IMN patients.The total cumulative dose CTX fluctuations in 0.15 to 0.2 g/kg.Once intravenous infusion at a dose of 0.6g,twice a month,and continuous use for 6months.Then,once 3 months.These two groups were given corticosteroids 0.75mg/(kg·d)initially,and regularly reducing the dose step by step.The patients were followed up for24 months.Result:After 24 months of treatment,the 24 hours urinary protein quantitation,ALB and TP of the patients in these two groups were improved significantly(p<0.01). After the treatment of 6 months and18 months,the total remission rate in TAC group were apparently higher than CTX group(p<0.05).After the treatment of 12 months and 24 months,the total remission rate between these two groups was approximate,with no statistical difference(p>0.05).After the treatment of 24 months,the complete remission rate in TAC group was apparently higher than CTX group(p<0.05).After the treatment of 18 months,the relapse rate in CTX group was apparently higher than TAC group(p<0.05).Treatment for 6 months and 12 months was positive correlation between the TAC blood drug concentration and treatment effect(p<0.05).Treatment for 18 months and 24 months was no correlation between the TAC blood drug concentration and treatment effect(p>0.05).The TAC treatment group completed treatment for 6 months, 12 months, 18 months and 24 months,the average blood concentrations were 5.65ng/ml, 4.86ng/ml, 2.83ng/ml and2.71ng/ml.The effective blood drug concentration range fluctuations in3.1~8.5 ng/ml,3.1~7.6ng/ml,1.4~4.56ng/ml, 1.4~4.35ng/ml.During the treatment,the incidence of abnormal glucose metabolism in TAC group was higher than the CTX group, statistically significant(p<0.05).Conclusion:After 24 months treatment,the complete remission in TAC group was apparently higher than CTX group.Using tacrolimus combined with corticosteroids to treat IMN was much better than CTX group in short-trem inducing remission and the complete remission in long-term treatment were better than CTX group.Using long-term and low blood concentration to treat IMN,the relapse in TAC group was lower than CTX group.In TAC group,the main adverse reactions was abnormal glucose tolerance.The incidence of abnormal glucose tolerance in the TAC group was higher than in the CTX group.In CTX group,the main adverse reactions was abnormal liver function.更多还原