类肝素药物对2型糖尿病肾脏病患者疗效和安全性的Meta分析  

Efficacy and safety of heparinoids in patients with type 2 diabetic nephropathy:a meta-analysis

作　　者：何雷[1] 张逸 靳晶晶[1] 程美娟 张胜雷[1] 白亚玲[1] 徐金升[1] He Lei;Zhang Yi;Jin Jingjing;Cheng Meijuan;Zhang Shenglei;Bai Yaling;Xu Jinsheng(Hebei Provincial Key Laboratory of Vascular Calcification in Kidney Disease,Hebei Provincial Clinical Research Center for Chronic Kidney Disease,Department of Nephrology,Fourth Hospital,Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北省慢性肾病临床医学研究中心,河北省肾脏病血管钙化重点实验室,河北医科大学第四医院肾内科,石家庄050011

出　　处：《中华糖尿病杂志》2024年第8期871-880,共10页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：河北省医学技术跟踪项目(G2018050);河北省重点研发计划项目(20377704D);河北省科技计划项目(16397733D);河北省慢性肾病临床医学研究中心创新能力提升(20577701D)。

摘　　要：目的系统评价类肝素药物对2型糖尿病肾脏病患者的疗效和安全性。方法检索美国国立医学图书馆数据库(PubMed)、荷兰医学文摘数据库(Embase)、循证医学数据库(the Cochrane Library)、中国期刊全文数据库(CNKI)、万方数据库、维普数据库和中国生物医学文献数据库(CBM),收集比较类肝素(类肝素组)和安慰剂或空白对照(对照组)治疗2型糖尿病肾脏病疗效及安全性的随机对照试验(RCT)及观察性研究,检索时限均为建库至2023年10月。按照纳排标准进行文献筛选,并从文献中提取资料和评价被纳入研究的偏倚风险后,采用RevMan 5.3及Stata 17.0软件进行Meta分析。结果共纳入22项研究,包含3800例患者。Meta分析结果显示,类肝素药物能够降低2型糖尿病肾脏病患者的尿白蛋白排泄率(SMD=-0.65,95%CI-0.98~-0.31,P<0.001)。进一步亚组分析显示,在亚洲患者中,类肝素药物降低尿蛋白的作用优于对照组(SMD=-0.48,95%CI-0.72~-0.24,P<0.001),而在欧洲患者中,没有观察到这种优势(SMD=-0.25,95%CI-0.62~0.13,P=0.190)。类肝素组和对照组在降低2型糖尿病肾脏病患者的血清肌酐(SMD=-0.08,95%CI-0.31~0.16,P=0.520)、血压[收缩压:WMD=-1.56 mmHg(1 mmHg=0.133 kPa),95%CI-3.66~0.55 mmHg,P=0.150;舒张压:WMD=-0.16 mmHg,95%CI-1.29~0.96 mmHg,P=0.780]、空腹血糖(SMD=-0.05,95%CI-0.24~0.14,P=0.600)以及糖化血红蛋白(WMD=-0.07%,95%CI-0.24%~0.10%,P=0.420)差异均无统计学意义。安全性方面,类肝素药物不增加注射部位血肿、恶性心血管事件等不良事件发生率(RR=1.11,95%CI 0.97~1.28,P=0.120)。结论类肝素药物可有效降低2型糖尿病肾脏病患者的尿蛋白水平,尤其是在亚洲患者中效果更显著,且在治疗过程中无明显不良反应。Objective To systematically evaluate the efficacy and safety of heparinoids in the treatment of patients with type 2 diabetic nephropathy.Methods Databases including PubMed,Embase,the Cochrane Library,China national knowledge infrastructure(CNKI),Wanfang,VIP and China biomedical literature(CBM)were searched for randomized controlled trials(RCT)and observational studies of the efficacy and safety of heparinoids in the treatment of type 2 diabetic nephropathy from inception to October 2023.Meta-analysis was performed using RevMan 5.3 and Stata 17.0 software after the literature was screened according to the exclusion criteria,data were extracted from the literature,and the risk of bias was evaluated.Results A total of 22 trials with 3800 patients were included.The results of the meta-analysis showed that heparinoids could significantly reduce urinary albumin excretion in patients with type 2 diabetic kidney disease(SMD=-0.65,95%CI-0.98--0.31,P<0.001).Subgroup analysis showed that heparinoids had an advantage over the control group in reducing urinary albumin excretion in Asian patients(SMD=-0.48,95%CI-0.72--0.24,P<0.001),while no such advantage was observed in Europeans(SMD=-0.25,95%CI-0.62-0.13,P=0.190).There was no significant difference between the heparinoid group and the control group in serum creatinine(SMD=-0.08,95%CI-0.31-0.16,P=0.520),blood pressure[systolic blood pressure:WMD=-1.56 mmHg(1 mmHg=0.133 kPa),95%CI-3.66-0.55 mmHg,P=0.150,diastolic blood pressure:WMD=-0.16 mmHg,95%CI-1.29-0.96 mmHg,P=0.780],fasting plasma glucose(SMD=-0.05,95%CI-0.24-0.14,P=0.600)and glycated hemoglobin A 1c(HbA 1c)(WMD=-0.07%,95%CI-0.24%-0.10%,P=0.420)in patients with type 2 diabetic nephropathy.In terms of safety,heparinoids did not increase the incidence of adverse events such as injection site hematoma and malignant cardiovascular events(RR=1.11,95%CI 0.97-1.28,P=0.120).ConclusionHeparinoids can effectively reduce the level of urinary albumin in patients with type 2 diabetic nephropathy,particularly in Asian patients,and th

关 键 词：糖尿病 2型 糖尿病肾病 类肝素 META分析 疗效 安全性 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]