A Meta-Analysis of the Clinical Efficacy of TCM Decoctions Made from Formulas in the Liuwei Dihuang Wan Categorized Formulas in Treating Diabetic Nephropathy Proteinuria

Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2018, Article ID 2427301, 10 pages https://doi.org/10.1155/2018/2427301 Review Article A Meta-Analysis of the Clinical Efficacy of TCM Decoctions Made from Formulas in the Liuwei Dihuang Wan Categorized Formulas in Treating Diabetic Nephropathy Proteinuria Xue Gao ,1,2 Jianwei Shang ,1 Hongfang Liu 1 2 ,1 and Borui Yu1 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China Beijing University of Chinese Medicine, Beijing 100029, China Correspondence should be addressed to Hongfang Liu; lhf Received 22 May 2018; Revised 21 August 2018; Accepted 14 September 2018; Published 26 September 2018 Academic Editor: Takao Namiki Copyright © 2018 Xue Gao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Diabetic nephropathy (DN) is one of the microvascular complications of diabetes mellitus. Proteinuria is the most important clinical characteristics of DN and an independent risk factor for disease progression of DN; reducing urine protein is the primary target of treatment strategies for DN. Liuwei Dihuang Wan Categorized Formulas (LDWCFs), a group of classic traditional Chinese medicine (TCM) formulas aiming at “kidney -tonifying”, have been widely used in the treatment of DN. This study aimed to obtain a comprehensive understanding of the TCM method “kidney-tonifying” in the treatment of DN by conducting a meta-analysis to analyze the clinical efficacy of decoctions made from the LDWCFs in the treatment of DN proteinuria. Methods. CNKI, Wanfang, Weipu, CBM, PubMed, Embase, and the Cochrane Library were searched; 14 studies were included in the meta-analysis. Results. The results showed that the overall efficacy of the LDWCFs in treating DN was significantly better than that of the comparators (OR 2.87, 95% CI 1.98–4.15, P<0.00001). These formulas showed better efficacy than the comparators in reducing 24-hour urinary protein level (MD 0.12, 95% CI 0.06–0.17, P<0.0001) and in reducing urine microalbumin excretion rate (SMD 0.87, 95% CI 0.41–1.32, P<0.0002). No serious adverse reactions were reported. Conclusions. TCM formulas included in the LDWCFs are safe and effective in the treatment of DN proteinuria. These findings suggested that the TCM therapeutic principle of “kidney-tonifying” is a valuable addition to the treatment strategies for DN. 1. Introduction Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus (DM) [1]. Proteinuria is the most important clinical characteristic of DN and an independent risk factor of disease progression [2]; the presence of microalbuminuria can increase allcause mortality in patients with DM [3]. Current therapeutic strategies for DN are based on lifestyle and diet habits changing, blood glucose and blood pressure control, and dyslipidemia correction [4]. Although many studies in recent years have confirmed the therapeutic effect of various medications including vitamin D [5] and immunosuppressant tacrolimus [6, 7] on reducing DN proteinuria and delaying disease progression, only the angiotensinconverting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) are recommended for clinical use. However, the use of ACEI/ARBs has limitations. It has been found that ACEI/ARBs are beneficial for patients with diabetics and hypertension who have an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 and a urinary albumincreatinine ratio (UACR) of ⩾300 mg/g. For these patients, ACEI/ARBs can delay the progression of chronic kidney disease (CKD). For patients with normal blood pressure, ACEI/ARBs are not preventive medication for diabetesinduced kidney injury [4]. Traditional Chinese medicine (TCM) demonstrates definite clinical efficacy in the treatment of DN proteinuria. Various TCM extracts or compound preparations have shown confirmed protective effects on the kidney [8–11]. According to the theory of TCM, the disease origin of DN is mainly in the “kidney”; the debilitating “kidney” and the stagnation 2 Evidence-Based Complementary and Alternative Medicine of the “kidney collateral” are critical to the pathogenesis of DN [12–16]. So the formula prescription principle “kidneytonifying” plays an important role in the treatment of DN. TCM formulas included in the Liuwei Dihuang Wan Categorized Formulas (LDWCFs) are classical reputable recipes used in TCM. The key ingredients of these formulas are prepared (dried and cooked) root of Rehmannia glutinosa, fruit of common Macrocarpium (syn. Cornus), underground tuber of Dioscorea batatas (Chinese yam), dried root bark of Paeonia suffruticosa (tree peony), prepared sclerotium of Wolfiporia extensa (syn. Poria cocos), and dried rhizome of Alisma plantago-aquatica (common water-plantain). Zhang Zhongjing (approx. AD 150-219) proposed the use of Shenqi Wan for the treatment of DN in his book “Synopsis of Prescriptions of the Golden Chamber”. By the Song Dynasty, Qian Yi (approx. AD 1032-1117) modified the formula of Shenqi Wan and developed the formula of Liuwei Dihuang Wan. In the following centuries, various formulas such as Zhi Bai Dihuang Wan, Gui Fu Dihuang Wan, and Jisheng Shenqi Wan were derived. These formulas consist of the LDWCFs, aiming on treating the “kidney” with different therapeutic focuses, i.e., “fortifying and replenishing kidney yin”, “fortifying and replenishing kidney yang”, or “fortifying and replenishing kidney qi”. Since ancient times, LDWCFs have been the most widely used TCM formulas in the treatment of DN [17, 18]. Experimental studies confirmed that LDWCFs has a protective effect on renal interstitial and glomerular injuries [19–23]. Therefore, in order to obtain a comprehensive understanding of the TCM “kidney-tonifying” method in the treatment of DN, a meta-analysis was carried out to analyze the clinical efficacy of decoctions made from the LDWCFs in the treatment of DN proteinuria. TCM decoctions from LDWCFs versus basic treatment + TCM placebo. Basic treatment included life style change and medications for blood glucose control. 2. Materials and Methods 2.1. Database Search. In this study, the following databases were searched: CNKI (http://www.cnki.net/), Wanfang (http:// www.wanfangdata.com.cn/index.html), Weipu (http://www .cqvip.com/), Chinese Biomedical Literature Database (CBM, http://www.sinomed.ac.cn/), PubMed, Embase, and Cochrane Library. The time frame was from the inception of the individual database to February 2018. The search terms used included (“diabetic nephropathy” OR “diabetic renal disease” OR “diabetic proteinuria”) AND (“dihuangwan” OR “liuweidihuangwan” OR “renqiqiwan” OR “jinkuishenqiwan”) AND “randomized control.” 2.2. Inclusion Criteria. Publications meeting the following criteria were incl (...truncated)