Johannah Linda Shergis1, Lihong Yang2, Anthony Lin Zhang3, Xinfeng Guo4, Lei Zhang5, Shuzhen Zhou6, Lu Zeng7, Wei Mao8, Charlie Changli Xue9. 1. The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology, Melbourne, 3083, Australia. Electronic address: johannah.shergis@rmit.edu.au. 2. The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China; The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology, Melbourne, 3083, Australia. Electronic address: lihongyang@gzucm.edu.cn. 3. The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology, Melbourne, 3083, Australia. Electronic address: tong.zhang@rmit.edu.au. 4. The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China; The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology, Melbourne, 3083, Australia. Electronic address: drguoxinfeng@163.com. 5. The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China. Electronic address: zlbread@126.com. 6. The Second Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: 309637010@qq.com. 7. The Second Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: 2994291285@qq.com. 8. The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China. Electronic address: weimao@gzucm.edu.cn. 9. The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China; The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology, Melbourne, 3083, Australia. Electronic address: charlie.xue@rmit.edu.au.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Historical literature and pharmacological studies both suggest that Astragalus membranaceus (A. membranaceus) holds potential benefits for diabetic kidney disease (DKD), which is a growing burden with limited proven renal protective options. AIM OF THE STUDY: An updated systematic review was conducted to evaluate the efficacy and safety of A. membranaceus preparations as an adjunctive therapy to conventional therapies for DKD. METHODS: Nine databases and five clinical trial registries were searched for randomized controlled trials (RCTs) of A. membranaceus preparations added to conventional therapies compared with conventional therapies alone for people with DKD. Study screening, data collection, and quality assessment were performed independently by two reviewers. Estimated effects were pooled as mean differences or standardized mean differences with 95% confidence intervals by using a random-effects model. RESULTS: Sixty-six studies, involving 4785 DKD participants, were included. The quality of the included studies was low due to methodological shortfalls. Meta-analysis showed that additional use of A. membranaceus injection reduced more albuminuria (32 RCTs, 2253 participants; SMD: 2.05 [-2.49, -1.61], I2 = 94%), proteinuria (26 RCTs, 1812 participants; SMD: 1.85 [-2.34, -1.37], I2 = 95%), and serum creatinine levels (32 RCTs, 2880 participants; -14.78 μmol/L [-19.22, -10.33], I2 = 97%) than conventional therapies alone did. An anti-albuminuria effect was also observed in the oral A. membranaceus preparation group (four RCTs, 236 participants; SMD: 1.27 [-1.82, -0.73], I2 = 73%). Meta-regression suggested that the treatment effect of A. membranaceus injection was associated with the baseline serum creatinine level. The adverse-events profile was similar between the additional A. membranaceus and control groups. CONCLUSION: The low quality of evidence suggested that adjunctive use of A. membranaceus preparations in addition to conventional therapies may be effective and tolerated for short-term reduction of albuminuria, proteinuria, and serum creatinine in DKD patients. The findings should be considered with caution due to the lack of high-quality RCTs and significant heterogeneity and publication bias. Further RCTs are needed to confirm the long-term efficacy and safety of A. membranaceus preparations, especially of the oral form, in patient-important outcomes.
ETHNOPHARMACOLOGICAL RELEVANCE: Historical literature and pharmacological studies both suggest that Astragalus membranaceus (A. membranaceus) holds potential benefits for diabetic kidney disease (DKD), which is a growing burden with limited proven renal protective options. AIM OF THE STUDY: An updated systematic review was conducted to evaluate the efficacy and safety of A. membranaceus preparations as an adjunctive therapy to conventional therapies for DKD. METHODS: Nine databases and five clinical trial registries were searched for randomized controlled trials (RCTs) of A. membranaceus preparations added to conventional therapies compared with conventional therapies alone for people with DKD. Study screening, data collection, and quality assessment were performed independently by two reviewers. Estimated effects were pooled as mean differences or standardized mean differences with 95% confidence intervals by using a random-effects model. RESULTS: Sixty-six studies, involving 4785 DKD participants, were included. The quality of the included studies was low due to methodological shortfalls. Meta-analysis showed that additional use of A. membranaceus injection reduced more albuminuria (32 RCTs, 2253 participants; SMD: 2.05 [-2.49, -1.61], I2 = 94%), proteinuria (26 RCTs, 1812 participants; SMD: 1.85 [-2.34, -1.37], I2 = 95%), and serum creatinine levels (32 RCTs, 2880 participants; -14.78 μmol/L [-19.22, -10.33], I2 = 97%) than conventional therapies alone did. An anti-albuminuria effect was also observed in the oral A. membranaceus preparation group (four RCTs, 236 participants; SMD: 1.27 [-1.82, -0.73], I2 = 73%). Meta-regression suggested that the treatment effect of A. membranaceus injection was associated with the baseline serum creatinine level. The adverse-events profile was similar between the additional A. membranaceus and control groups. CONCLUSION: The low quality of evidence suggested that adjunctive use of A. membranaceus preparations in addition to conventional therapies may be effective and tolerated for short-term reduction of albuminuria, proteinuria, and serum creatinine in DKD patients. The findings should be considered with caution due to the lack of high-quality RCTs and significant heterogeneity and publication bias. Further RCTs are needed to confirm the long-term efficacy and safety of A. membranaceus preparations, especially of the oral form, in patient-important outcomes.