硫胺素联合叶酸治疗维持性血液透析患者认知损害的研究  

Thiamine combined with folic acid in the treatment of cognitive impairment in maintenance hemodialysis patients

作　　者：曾小君 谢可炜[1] 李萍[1] 刘上[1] 仇婷 颜佳毅[1] 潘舒婷 林岩[3] 袁江姿[1] 庞慧华[1] 张伟明[1] 顾乐怡[1] 陆任华[1] ZENG Xiaojun;XIE Kewei;LI Ping;LIU Shang;QIU Ting;YAN Jiayi;PAN Shuting;LIN Yan;YUAN Jiangzi;PANG Huihua;ZHANG Weiming;GU Leyi;LU Renhua(Department of Nephrology,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;不详)

机构地区：[1]上海交通大学医学院附属仁济医院肾脏科,上海200127 [2]上海交通大学医学院附属仁济医院临床研究中心,上海200127 [3]上海交通大学医学院附属仁济医院神经内科,上海200127

出　　处：《上海医学》2022年第1期3-9,共7页Shanghai Medical Journal

基　　金：上海申康医院发展中心临床三年行动计划(SHDC2020CR4004);2019年度上海交通大学医学院附属仁济医院科研种子基金培养计划(RJZZ19-04);中华医学会临床医学科研专项(18020030782)。

摘　　要：目的探讨应用硫胺素联合叶酸治疗行维持性血液透析(MHD)继发认知损害(CI)的终末期肾病(ESRD)患者的有效性和安全性。方法采用前瞻性、随机、对照、开放标签的研究方法,收集在上海交通大学医学院附属仁济医院行MHD(透析时间≥3个月)的ESRD患者的临床资料,若蒙特利尔认知评估量表(MoCA量表)评分<26分(如受试者教育年限<12年,MoCA量表评分<25分)则判定该患者继发CI。按照随机分组法将患者分为治疗组(硫胺素90 mg/d联合叶酸30 mg/d的强化治疗)和对照组(不予任何干预),每组各25例。记录患者的基线期、随访至48周和96周时的实验室检查结果和血液透析(HD)相关资料,以及患者的MoCA量表评分,血硫胺素、叶酸和同型半胱氨酸水平;并评估患者的疗效指标、生存情况和不良事件发生情况。结果治疗组血磷水平显著高于对照组(P<0.05),两组间其他实验室指标的差异均无统计学意义(P值均>0.05)。随访至96周时,治疗组患者的MoCA量表评分和血叶酸水平均显著高于基线期(t=6.86、5.67,P值均<0.001)。组间分析显示,随访至96周时治疗组患者的MoCA量表评分、血硫胺和血叶酸水平均显著高于对照组同时间点(F=44.89、7.29、24.31,P值均<0.01),而血同型半胱氨酸水平显著低于对照组同时间点(F=6.42,P=0.016)。生存曲线分析提示,随访至96周时治疗组患者的生存率显著高于对照组(P=0.048)。心脑血管疾病(9/12)为患者主要的死亡原因。随访期间两组不良事件总发生率为66.0%(33/50),对照组不良事件发生率(26/33,78.8%)显著高于治疗组(7/33,21.2%,P<0.001);其中,治疗组心脑血管疾病的发生率为2/7,显著低于对照组的46.2%(12/26,P=0.005)。结论硫胺素联合叶酸强化治疗可显著改善行MHD继发CI的ESRD患者的MoCA量表评分,并给患者带来生存获益。Objective To explore the effectiveness and safety of thiamine combined with folic acid in the treatment of cognitive impairment(CI)in patients with end-stage renal disease(ESRD)treated by maintenance hemodialysis(MHD).Methods Patients with ESRD who underwent MHD(dialysis time≥3 months)in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this prospective,randomized,controlled,and open-label study.Once the score of Montreal Connitive Assessment(MoCA)was less than 26(if subject’s education was less than 12 years,MoCA score less than 25),the patient was diagnosed as secondary CI.The patients were randomly divided into treatment group(intensive treatment of thiamine 90 mg/d combined with folic acid 30 mg/d,n=25)and control group(no intervention,n=25).Laboratory examination results and HD-related data,as well as MoCA score,serum thiamine,folic acid and homocysteine levels were recorded at baseline,48 weeks and 96 weeks after treatment.Efficacy indicators,survival status and occurrence of adverse events were evaluated.Results Serum phosphorus level of the treatment group was significantly higher than that of the control group(P<0.05),and there were no significant differences in other laboratory indexes between the two groups(all P>0.05).The MoCA score and serum folate level of the treatment group at 96 weeks of follow-up were significantly higher than those in the baseline period(t=6.86,5.67,both P<0.001).At the follow-up of 96 weeks,compared with those in the control group,the MoCA score,serum thiamine and folate levels were significantly increased in the treatment group(F=44.89,7.29,24.31,all P<0.01),and homocysteine level was significantly decreased(F=6.42,P=0.016).The survival rate of the treatment group was significantly higher than that of the control group at the 96-week follow-up(P=0.048).Cardiovascular and cerebrovascular diseases were the main cause of death(9/12).A total of 33 adverse events(66.0%)occurred during follow up.The incidence of adverse events in the

关 键 词：终末期肾脏疾病 认知功能 维生素B 氧化应激 生存 

分 类 号：R692.5[医药卫生—泌尿科学]