雷公藤多甙联合RAS阻断剂治疗糖尿病肾病的临床研究

发布时间：2018-11-22 16:50

【摘要】：研究背景糖尿病肾病(Diabetic Kidney Disease,DKD)是糖尿病最常见的并发症之一,也是终末期肾衰竭主要原因之一。近年来,中国糖尿病和糖尿病肾病的发病率呈上升趋势。DKD目前尚无有效的治疗方法和手段,主要强调早期干预各种危险因素,包括积极控制高血糖,严格控制血压,纠正脂质代谢紊乱,抗血小板聚集,治疗肥胖,戒烟等。多项大型临床研究已证实肾素-血管紧张素系统(Renin-angiotensin system,RAS)阻断剂包括血管紧张素转化酶抑制剂(Angiotension-converting Enzyme Inhibitors,ACEI)或血管紧张素Ⅱ受体拮抗剂(AngiotensinⅡ Receptor Antagonists,ARB)除了能降低血压外,还可降低尿蛋白水平,带来额外的延缓肾病进展的获益,但其亦具有高血钾、一过性引起肾小球滤过率下降的副作用。多项临床研究和动物研究证实,雷公藤多甙具有抗炎、免疫抑制、保护足突细胞和降低尿蛋白作用,虽有研究发现雷公藤多甙可降低糖尿病肾病尿蛋白水平,但随访时间短,目前关于雷公藤多甙联合RAS阻断剂治疗DKD的研究有限,雷公藤多甙用于糖尿病肾病进展到慢性肾脏病(Chronic Kidney Disease,CKD)3期以上患者尚缺乏临床资料。本研究旨在初步探讨雷公藤多甙联合RAS阻断剂治疗DKD的疗效和安全性,并初步观察雷公藤多甙对糖尿病肾病CKD 3期患者的疗效。研究目的1、研究雷公藤多甙联合RAS阻断剂治疗DKD的疗效和安全性。2、探索雷公藤多甙联合RAS阻断剂对糖尿病肾病CKD 3期患者的疗效。研究方法2013年至2017年就诊并在北京协和医院肾内科门诊随诊的患者中,选取病历资料保存完整,符合临床糖尿病肾病IV期,接受DKD正规治疗包括RAS阻断剂至少3月尿微量白蛋白肌酐比(Albumin-to-creatinine ratio,ACR)无下降,加用雷公藤多甙治疗的患者作为研究对象,对符合上述条件并规律随访的患者进行分析,收集临床及随访资料,回顾性分析患者基线及用药第1、3、6、12个月的临床指标、实验室检查(包括ACR、血清肌酐等)、治疗及预后情况。研究结果1、入选本研究 30 名患者,年龄 57.5±9.6 岁,尿 ACR 2774.5±2012.6mg/gCr,血清肌酐(Serum creatinine,SCr)150.7±95.1umol/L,估测肾小球滤过率(estimated GFR,eGFR)56.9±27.8 ml/min/1.73m2。随访 12 个月,治疗第 1、3、6、12 个月 ACR 下降率分别为 38.1%、57.8%、51.0%、61.7%(其中第 3、6、12个月p0.05)。患者治疗后第12月eGFR较基线下降15.1±1.0ml/min/l.73m2,未见雷公藤多甙联合RAS阻断剂有明确肾功能的保护作用。2、糖尿病肾病CKD3期患者17人,治疗第1、3、6、12个月ACR下降率分别为35.4%、50.5%、43.6%、57.5%(各时间点p0.05);eGFR第12月较基线下降7.08 ml/min/1.73m2,平均每月下降 0.59 ml/min/l.73m2(p0.05)。3、患者血清白蛋白(Alb)第1、3、6、12个月下降分别较基线下降3.7(p0.05)、3.0、1.9、1.4 g/L,至第12月Alb逐渐上升至接近基线水平,治疗期间出现消化道反应(恶心、呕吐)者2例,单纯疱疹者1例,未观察到其他药物副作用。研究结论1、糖尿病肾病患者在RAS阻断剂治疗基础上加用雷公藤多甙可进一步降低ACR水平。2、对CKD 3期糖尿病肾病患者在RAS阻断剂治疗基础上加用雷公藤多甙可进一步降低ACR水平,并可能对eGFR的下降有延缓作用。
[Abstract]:Background Diabetic nephropathy (DKD) is one of the most common complications of diabetes, and is one of the main causes of end-stage renal failure. In recent years, the incidence of diabetes and diabetic nephropathy in China is on the rise. DKD currently has no effective treatment methods and means, mainly emphasizing the early intervention of various risk factors, including active control of hyperglycemia, strict control of blood pressure, correction of lipid metabolism disorders, anti-platelet aggregation, and the treatment of obesity, smoking cessation, and the like. A number of large clinical studies have confirmed that the renin-angiotensin system (RAS) blocker comprises an angiotensin converting enzyme inhibitor (ACEI) or a angiotensin II receptor antagonist (ARB), There is an additional benefit for delaying the progression of the kidney disease, but it also has a high blood potassium, an oversex effect that causes a decrease in the glomerular filtration rate. A number of clinical studies and animal studies have shown that the tripterygium wilfordii has the effects of anti-inflammation, immunosuppression, protection of the apophysis cells and the reduction of the urinary protein, although the study has shown that the triptolide can reduce the urinary protein level of the diabetic nephropathy, the follow-up time is short, At present, there is a limited study on the treatment of DKD by the combination of Tripterygium wilfordii and the RAS blocker, which is used in the treatment of diabetic nephropathy and the patients with chronic kidney disease (CKD) for more than 3 years still lack the clinical data. The aim of this study was to investigate the efficacy and safety of triptolide combined with RAS blocker in the treatment of DKD, and to observe the effect of triptolide on the patients with CKD stage 3 of diabetic nephropathy. Objective To study the efficacy and safety of triptolide combined with RAS blocker in the treatment of DKD. The method of the study was to take a visit from 2013 to 2017 and to select the medical record data to be intact and to meet the stage IV of the clinical diabetic nephropathy. The normal treatment of the DKD, including the RAS blocking agent at least 3 months, has no decrease in the ratio of the microalbumins-to-creatinine ratio (ACR). The patients treated with Tripterygium wilfordii were used as the subject of the study, and the patients who met the above conditions and regularly followed up were analyzed, the clinical and follow-up data were collected, and the clinical indicators, laboratory tests (including ACR, serum myoglobin, etc.) of the baseline and the first, 3, 6 and 12 months of the patient were retrospectively analyzed. Treatment and prognosis. The results of the study were as follows: 1. In the study, 30 patients were enrolled in this study. The age of 57. 5-9. 6, the urinary ACR 2774. 5-2012. 6mg/ gCr, Serum creatinine, SCr. 7-95.1umol/ L, estimated glomerular filtration rate (eGFR) of 55.6 mg/ gCr, and estimated glomerular filtration rate (eGFR) of 55.6 mg/ min/ 1. 73m2. The rate of ACR in treatment group 1, 3, 6 and 12 months was 38. 1%, 57. 8%, 51. 0%, 61. 7% in 12 months of follow-up. The decrease of eGFR in the first, third, sixth and 12th month was 30.4%, 54.5%, 43.6%, 55.7% (time point p0.05). The baseline decreased from baseline to 7.08 ml/ min/ 1. 73m2 in the month of eGFR, and the mean monthly decrease was 0.59 ml/ min/ l. 73m2 (p0.05). 3. The decrease of serum albumin (Alb) in the first, third, 6th and 12th months of the patient decreased from baseline to 3.7 (p0.05), 3.0, 1.9, 1.4 g/ L, to December Alb gradually to close to the baseline level, and 2 cases of the digestive tract reaction (nausea and vomiting) occurred during the treatment period. One case of herpes simplex, no side effects of other drugs were observed. Conclusion: 1. The patients with diabetic nephropathy can further decrease the level of ACR by using Tripterygium wilfordii on the basis of the treatment of RAS blocker. 2. The application of triptolide on the treatment of patients with CKD-3 diabetic nephropathy can further decrease the level of ACR. and may slow down the decline in eGFR.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R692.9

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