DataSheet1_Efficacy and safety of Abelmoschus manihot capsule combined with ACEI/ARB on diabetic kidney disease: a systematic review and meta analysis.ZIP

Background: Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes, with the incidence rate increasing yearly, which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease. Abelmoschus Manihot capsule, as a proprietary Chinese patent medicine, is widely used for treating CKD in China. Currently, the combination of Abelmoschus Manihot (AM) capsule and renin-angiotensin-aldosterone system inhibitor (RASI) has gained popularity as a treatment option for DKD, with more and more randomized control trials (RCTs) in progress. However, the high-quality clinical evidence supporting its application in DKD is still insufficient.
Aim of the study: To comprehensively and systematically evaluate the efficacy and safety of AM capsule combined with RASI in the treatment of DKD.
Materials and methods: English and Chinese databases such as Pubmed, Cochrane Library, Embase, CNKI, SinoMed, WF, and VIP were searched to collect the RCTs of AM capsule in treatment of DKD. Then Two investigators independently reviewed and extracted data from the RCTs which met the inclusion criteria. The quality of the data was assessed using the Cochrane risk of bias assessment tool, and meta-analysis was performed using RevMan 5.4 software.
Results: 32 RCTs with a total of 2,881 DKD patients (1,442 in the treatment group and 1,439 in the control group) were included. The study results showed that AM capsule combined with RASI could be more effective in decreasing 24h-UTP [MD = −442.05, 95% CI (−609.72, −274.38), p < 0.00001], UAER [MD = −30.53, 95% CI (−39.10, −21.96), p < 0.00001], UACR [MD = −157.93, 95% CI (−288.60, −27.25), p < 0.00001], Scr [MD = −6.80, 95% CI (−9.85, −3.74), p < 0.0001], and BUN [MD = −0.59, 95% CI (−1.07, −0.12), p = 0.01], compared to using RASI alone. According to the subgroup analyses, the combination of AM and ARB seems to be more effective in reducing UAER than the combination of ACEI, and the addition of AM may achieve a more significant clinical effect on decreasing Scr for DKD patients with 24h-UTP>2 g or Scr>110–133 μmol/L and >133 μmol/L. Furthermore, no additional adverse reactions were observed in the combination group [OR = 1.06; 95%CI: (0.66, 1.69), p = 0.82].
Conclusion: Combining AM with RASI may be a superior strategy for DKD treatment compared to RASI monotherapy. However, due to significant heterogeneity, the results should be interpreted with great caution, and more high-quality RCTs with multi-centers, different stages of DKD, large sample sizes, and long follow-up periods are still needed to improve the evidence quality of AM for DKD in the future.
Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails; Identifier CRD42022351422

背景：糖尿病肾病（Diabetic kidney disease, DKD）是糖尿病最严重的微血管并发症之一，发病率逐年攀升，亦是慢性肾脏病（chronic kidney disease, CKD）及终末期肾病的首要致病原因。黄葵胶囊（Abelmoschus Manihot capsule）作为国内临床常用的中成药，广泛应用于慢性肾脏病的治疗。当前，黄葵胶囊联合肾素-血管紧张素-醛固酮系统抑制剂（renin-angiotensin-aldosterone system inhibitor, RASI）已成为糖尿病肾病的主流治疗方案之一，相关随机对照试验（randomized control trials, RCTs）也日益增多。然而，支持其用于糖尿病肾病治疗的高质量临床证据仍较为匮乏。
研究目的：本研究旨在全面系统评价黄葵胶囊联合肾素-血管紧张素-醛固酮系统抑制剂治疗糖尿病肾病的有效性与安全性。
材料与方法：检索PubMed、Cochrane Library、Embase、中国知网（CNKI）、中国生物医学文献数据库（SinoMed）、万方数据知识服务平台（WF）、维普资讯网（VIP）等中英文数据库，收集黄葵胶囊治疗糖尿病肾病的随机对照试验。由2名研究者独立对符合纳入标准的随机对照试验进行文献筛选与数据提取。采用Cochrane偏倚风险评估工具对纳入研究的质量进行评价，并使用RevMan 5.4软件开展Meta分析。
结果：最终纳入32项随机对照试验，共计2881例糖尿病肾病患者（治疗组1442例，对照组1439例）。研究结果显示，相较于单用肾素-血管紧张素-醛固酮系统抑制剂，黄葵胶囊联合该类药物可更显著降低24小时尿总蛋白（24h-UTP）[MD = −442.05, 95%CI (−609.72, −274.38), p < 0.00001]、尿白蛋白排泄率（UAER）[MD = −30.53, 95%CI (−39.10, −21.96), p < 0.00001]、尿白蛋白肌酐比值（UACR）[MD = −157.93, 95%CI (−288.60, −27.25), p < 0.00001]、血肌酐（Scr）[MD = −6.80, 95%CI (−9.85, −3.74), p < 0.0001]及血尿素氮（BUN）[MD = −0.59, 95%CI (−1.07, −0.12), p = 0.01]。亚组分析结果表明，相较于血管紧张素转换酶抑制剂（ACEI）联合方案，黄葵胶囊与血管紧张素Ⅱ受体拮抗剂（ARB）联合方案在降低尿白蛋白排泄率方面效果更优；对于24小时尿总蛋白>2 g或血肌酐>110–133 μmol/L、>133 μmol/L的糖尿病肾病患者，加用黄葵胶囊可更显著改善其血肌酐水平。此外，联合治疗组未观察到额外的不良反应发生[OR = 1.06; 95%CI: (0.66, 1.69), p = 0.82]。
结论：相较于单用肾素-血管紧张素-醛固酮系统抑制剂，黄葵胶囊联合该类药物或为糖尿病肾病更优的治疗策略。但由于研究间存在显著异质性，解读该结果时需谨慎；未来仍需开展多中心、覆盖不同糖尿病肾病分期、大样本量且长期随访的高质量随机对照试验，以进一步提升黄葵胶囊治疗糖尿病肾病的证据等级。
系统评价注册信息：https://www.crd.york.ac.uk/PROSPERO/#recordDetails；标识符：CRD42022351422