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Chinese herbal medicine for diabetic kidney disease: a systematic review and meta-analysis of randomised placebo-controlled trials
  1. La Zhang1,2,
  2. Lihong Yang2,3,
  3. Johannah Shergis4,
  4. Lei Zhang1,
  5. Anthony Lin Zhang4,
  6. Xinfeng Guo2,3,
  7. Xindong Qin1,
  8. David Johnson5,6,
  9. Xusheng Liu1,
  10. Chuanjian Lu2,7,
  11. Charlie Changli Xue4,
  12. Wei Mao1
  1. 1 Nephrology Department, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
  2. 2 The China–Australia International Research Centre for Chinese Medicine, RMIT University, Melbourne, Victoria, Australia
  3. 3 Evidence-Based Medicine and Clinical Research Service Team, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
  4. 4 School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia
  5. 5 Australia Kidney Trials Network, University of Queensland, Brisbane, Queensland, Australia
  6. 6 Nephrology Department, Translational Research Institute, South Brisbane, Queensland, Australia
  7. 7 Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
  1. Correspondence to Dr Charlie Changli Xue; charlie.xue{at}rmit.edu.au and Professor Wei Mao; maowei1274{at}126.com

Abstract

Objectives To provide a broad evaluation of the efficacy and safety of oral Chinese herbal medicine (CHM) as an adjunctive treatment for diabetic kidney disease (DKD), including mortality, progression to end-stage kidney disease (ESKD), albuminuria, proteinuria and kidney function.

Design A systematic review and meta-analysis.

Methods Randomised controlled trials (RCTs) comparing oral CHM with placebo as an additional intervention to conventional treatments were retrieved from five English (Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Allied and Complementary Medicine Database and Cumulative Index of Nursing and Allied Health Literature) and four Chinese databases (China BioMedical Literature, China National Knowledge Infrastructure, Chonqing VIP and Wanfang) from inception to May 2018. RCTs recruiting adult DKD patients induced by primary diabetes were considered eligible, regardless of the form and ingredients of oral CHM. Mean difference (MD) or standardised mean difference (SMD) was used to analyse continuous variables and RR for dichotomous data.

Results From 7255 reports retrieved, 20 eligible studies involving 2719 DKD patients were included. CHM was associated with greater reduction of albuminuria than placebo, regardless of whether renin–angiotensin system (RAS) inhibitors were concurrently administered (SMD −0.56, 95% CI [−1.04 to –0.08], I2=64%, p=0.002) or not (SMD −0.92, 95% CI [−1.35 to –0.51], I2=87%, p<0.0001). When CHM was used as an adjunct to RAS inhibitors, estimated glomerular filtration rate was higher in the CHM than placebo group (MD 6.28 mL/min; 95% CI [2.42 to 10.14], I2=0%, p=0.001). The effects of CHM on progression to ESKD and mortality were uncertain due to low event rates. The reported adverse events in CHM group included digestive disorders, elevated liver enzyme level, infection, anaemia, hypertension and subarachnoid haemorrhage, but the report rates were low and similar to control groups. The favourable results of CHM should be balanced with the limitations of the included studies such as high heterogeneity, short follow-up periods, small numbers of clinical events and older patients with less advanced disease.

Conclusions Based on moderate to low quality evidence, CHM may have beneficial effects on renal function and albuminuria beyond that afforded by conventional treatment in adults with DKD. Further well-conducted, adequately powered trials with representative DKD populations are warranted to confirm the long-term effect of CHM, particularly on clinically relevant outcomes.

PROSPERO registration number CRD42015029293.

  • diabetic kidney disease
  • Chinese herbal medicine
  • complementary and alternative medicine
  • systematic review
  • meta-analysis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • CCX and WM contributed equally.

  • LaZ and LY contributed equally.

  • Contributors Research idea and study design: LaZ, CL, CCX and WM; data collection and screening: LaZ, LY, JS, XQ and ALZ; data extraction: LaZ, LY and JS; data analysis: LaZ and JS; risk of bias assessment: LaZ, LY, XG and ALZ; GRADE assessment: WM, LeiZ, LY, JS and DJ; manuscript writing: all authors; supervision and mentorship: CCX, XL and CL. Each author contributed important intellectual content during manuscript drafting and revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

  • Funding The project is jointly supported by the China–Australia International Research Centre for Chinese Medicine (CAIRCCM)—a joint initiative of RMIT University, Australia and the Guangdong Provincial Academy of Chinese Medical Sciences, China with additional funding support from the Ministry of Science & Technology of China (International Cooperation Project, Grant Number 2012DFA31760) and a grant from the National Natural Science Foundation of China (Grant Number 81603717).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data extracted from original studies and data used for meta-analysis are available on request.

  • Patient consent for publication Not required.

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